Identification
NameDaclatasvir
Accession NumberDB09102
TypeSmall Molecule
GroupsApproved
Description

Daclatasvir is a direct-acting antiviral agent against Hepatitis C Virus (HCV) used for the treatment of chronic HCV genotype 1 and 3 infection. It is marketed under the name DAKLINZA and is contained in daily oral tablets as the hydrochloride salt form . Hepatitis C is an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [8]. Daclatasvir was the first drug with demonstrated safety and therapeutic efficacy in treating HCV genotype 3 without the need for co-administration of interferon or Ribavirin. It exerts its antiviral action by preventing RNA replication and virion assembly via binding to NS5A, a nonstructural phosphoprotein encoded by HCV. Binding to the N-terminus of the D1 domain of NS5A prevents its interaction with host cell proteins and membranes required for virion replication complex assembly. Daclatasvir is shown to target both the cis- and trans-acting functions of NS5A and disrupts the function of new HCV replication complexes by modulating the NS5A phosphorylation status [3]. The most common critical NS5A amino acid substitutions that led to reduced susceptibility to daclatasvir therapy occured at position Q30 (Q30H/K/R) and M28 in genotype 1a patients and Y93H in genotype 3 patients.

According to 2017 American Association for the Study of Liver Diseases (AASLD), 60mg of daclatasvir is recommended with 400mg Sofosbuvir for genotype 1a/b patients with or without cirrhosis as second-line therapy. The same dosing regimen can be used as first-line therapy in patients with genotype 3 without cirrhosis and second-line therapy in genotype 3 patients with compensated cirrhosis. Combination therapies that include daclatasir can be used for challenging-to-treat patients who have HIV-1 coinfection, advanced cirrhosis, or post-liver transplant recurrence of HCV [9]. The therapy is intended to cure or achieve a sustained virologic response (SVR12), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [6].

Daclatasvir was FDA-approved in July 2015 for use with Sofosbuvir (Sovaldi) with or without Ribavirin to treat HCV genotype 1 and 3 infections. The SVR12 in HCV genotype 1a-infected treatment-naïve subjects without and with cirrhosis undergoing daclatasvir and Sofosbuvir therapy were 88% and 99%, respectively [FDA Label]. The same dosing regimen in treatment-naïve patients with HCV genotype 3 infection with or without cirrhosis achieved SVR12 rates of 71% and 98%, respectively [FDA Label].

Structure
Thumb
Synonyms
BMS-790052
External IDs BMS 790052 / BMS 790052-05 / BMS-790052-05 / EBP 883 / EBP-883
Product Ingredients
IngredientUNIICASInChI KeyDetails
Daclatasvir dihydrochloride50ZO25C11D 1009119-65-6BVZLLUDATICXCI-JMSCDMLISA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DaklinzaTablet30 mgOralBristol Myers Squibb2015-09-08Not applicableCanada
DaklinzaTablet60 mg/1OralE.R. Squibb & Sons, L.L.C.2015-07-27Not applicableUs
DaklinzaTablet60 mgOralBristol Myers Squibb2015-09-08Not applicableCanada
DaklinzaTablet90 mg/1OralE.R. Squibb & Sons, L.L.C.2016-05-18Not applicableUs
DaklinzaTablet30 mg/1OralE.R. Squibb & Sons, L.L.C.2015-07-27Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIILI2427F9CI
CAS number1009119-64-5
WeightAverage: 738.89
Monoisotopic: 738.385331362
Chemical FormulaC40H50N8O6
InChI KeyFKRSSPOQAMALKA-CUPIEXAXSA-N
InChI
InChI=1S/C40H50N8O6/c1-23(2)33(45-39(51)53-5)37(49)47-19-7-9-31(47)35-41-21-29(43-35)27-15-11-25(12-16-27)26-13-17-28(18-14-26)30-22-42-36(44-30)32-10-8-20-48(32)38(50)34(24(3)4)46-40(52)54-6/h11-18,21-24,31-34H,7-10,19-20H2,1-6H3,(H,41,43)(H,42,44)(H,45,51)(H,46,52)/t31-,32-,33-,34-/m0/s1
IUPAC Name
methyl N-[(2S)-1-[(2S)-2-[5-(4'-{2-[(2S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}-[1,1'-biphenyl]-4-yl)-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
SMILES
COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[[email protected]]1C1=NC=C(N1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CN=C(N1)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)OC)C(C)C
Pharmacology
Indication

Indicated for use with sofosbuvir, with or without ribavirin, for the treatment of chronic HCV genotype 1a/b or 3 infection. The dosing regimen of 60mg daclatasvir 60 mg with 400mg sofosbuvir once a day is recommended for both genontypes.

Resistance: Reduced susceptibility to daclatasvir was associated with the polymorphisms at NS5A amino acid positions M28, Q30, L31, and Y93 in genotypes 1a, 1b, and 3a patients. NS5A Resistance Testing is recommended for HCV genotype 1a-infected patients with cirrhosis prior to the initiaition of the treatment, as the risk of resistance development is higher in genotype 1a patients.

Structured Indications
Pharmacodynamics

Daclatasvir is a direct-acting antiviral agent that targets the NS5A and causes a decrease in serum HCV RNA levels. It disrupts HCV replication by specifically inhibiting the critical functions of an NS5A protein in the replication complex [3]. It is shown to cause downregulation of the hyperphosphorylation of NS5A. It does not appear to prolong the QT interval even when given at 3 times the maximum recommended dose.

Mechanism of action

NS5A is a viral nonstructural phospoprotein that is part of a functional replication complex in charge of viral RNA genome amplification on endoplasmic reticulum membranes. It has the ability to bind to HCV RNA. It is shown to have two distinct functions in HCV RNA replication based on phosphorylated states. Maintaining the HCV replication complex is mediated by the cis-acting function of basally phosphorylated NS5A and the trans-acting function of hyperphosphorylated NS5A modulates HCV assembly and infectious particle formation [3]. Daclatasvir is shown to disrupt hyperphosphorylated NS5A proteins thus interfere with the function of new HCV replication complexes. It is also reported that daclatasvir also blocks both intracellular viral RNA synthesis and virion assembly/secretion in vivo [2].

TargetKindPharmacological actionActionsOrganismUniProt ID
Nonstructural Protein 5A (NS5A)Proteinunknown
inhibitor
Hepatitis C Virus (HCV)not applicabledetails
Related Articles
Absorption

Studies demonstrated that peak plasma concentrations typically occurred within 2 hours after administration of multiple oral doses ranging from 1 - 100 mg once daily. Steady state is reached after approximately 4 days of once-daily daclatasvir administration. The absolute bioavailability of the tablet formulation is 67%.

Volume of distribution

The approximate volume of distribution of daclatasvir is 47 L in patients who was orally administered 60 mg tablet followed by 100 µg [13C,15N]-daclatasvir intravenously.

Protein binding

Daclatasvir is highly protein bound (99%).

Metabolism

Daclastavir is a substrate of CYP3A enzymes where its metabolism is predominantly mediated by CYP3A4 isoform. Oxidative pathways included δ-oxidation of the pyrrolidine moiety, resulting in ring opening to an aminoaldehyde intermediate followed by an intramolecular reaction between the aldehyde and the proximal imidazole nitrogen atom [7]. High proportion of the drug in the plasma (greater than 97%) is in the unchanged form.

Route of elimination

Approximately 88% of total dose of daclatasvir is eliminated into bile and feces in which 53% remains as unchanged form, while 6.6% of the total dose is eliminated primarily unchanged in the urine.

Half life

Following multiple dose administration of daclatasvir in HCV-infected subjects, with doses ranging from 1 mg to 100 mg once daily, the terminal elimination half-life of daclatasvir ranged from approximately 12 to 15 hours.

Clearance

In subjects who received daclatasvir 60 mg tablet orally followed by 100 µg radiolabeled daclatasvir intravenously, the total clearance was 4.2 L/h.

Toxicity

The most common adverse effects experienced in patients undergoing daclatasvir and sofosbuvir therapy include headache, fatigue, nausea and diarrhea. Similar side effects are seen when ribavirin is added, in addition to rash, insomnia, anemia, dizziness and somnolence. There are postmarketing cases that link serious symptomatic bradycardia with Daklinza when used in conjunction with sofosbuvir and amiodarone. Coadministration of these three drugs is not recommended unless there are no other alternatives.

Affected organisms
  • Hepatitis C Virus
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Daclatasvir.Approved
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Daclatasvir.Approved
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Daclatasvir.Approved, Vet Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Daclatasvir.Approved
AldosteroneThe serum concentration of Aldosterone can be increased when it is combined with Daclatasvir.Experimental
AlitretinoinThe serum concentration of Alitretinoin can be increased when it is combined with Daclatasvir.Approved, Investigational
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Daclatasvir.Approved, Investigational
AmiodaroneDaclatasvir may increase the bradycardic activities of Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Daclatasvir.Approved
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Daclatasvir.Approved
AprepitantThe serum concentration of Daclatasvir can be increased when it is combined with Aprepitant.Approved, Investigational
Arsenic trioxideThe serum concentration of Arsenic trioxide can be increased when it is combined with Daclatasvir.Approved, Investigational
AtazanavirThe serum concentration of Daclatasvir can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Atenolol can be increased when it is combined with Daclatasvir.Approved
AtomoxetineThe metabolism of Daclatasvir can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Daclatasvir.Approved
AxitinibThe serum concentration of Axitinib can be increased when it is combined with Daclatasvir.Approved, Investigational
BetamethasoneThe serum concentration of Betamethasone can be increased when it is combined with Daclatasvir.Approved, Vet Approved
BexaroteneThe serum concentration of Daclatasvir can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe serum concentration of Daclatasvir can be increased when it is combined with Boceprevir.Withdrawn
BortezomibThe metabolism of Daclatasvir can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Daclatasvir can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Daclatasvir.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Daclatasvir.Approved
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Daclatasvir.Approved, Investigational
CabazitaxelThe serum concentration of Cabazitaxel can be increased when it is combined with Daclatasvir.Approved
CaffeineThe serum concentration of Caffeine can be increased when it is combined with Daclatasvir.Approved
CamptothecinThe serum concentration of Camptothecin can be increased when it is combined with Daclatasvir.Experimental
CanagliflozinThe serum concentration of Canagliflozin can be increased when it is combined with Daclatasvir.Approved
CarbamazepineThe serum concentration of Daclatasvir can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarfilzomibThe serum concentration of Carfilzomib can be increased when it is combined with Daclatasvir.Approved
CeritinibThe serum concentration of Daclatasvir can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Daclatasvir.Withdrawn
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Daclatasvir.Approved, Vet Approved
CimetidineThe serum concentration of Cimetidine can be increased when it is combined with Daclatasvir.Approved
CiprofloxacinThe serum concentration of Ciprofloxacin can be increased when it is combined with Daclatasvir.Approved, Investigational
CisplatinThe serum concentration of Cisplatin can be increased when it is combined with Daclatasvir.Approved
CitalopramThe serum concentration of Citalopram can be increased when it is combined with Daclatasvir.Approved
ClarithromycinThe serum concentration of Daclatasvir can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Daclatasvir can be decreased when combined with Clemastine.Approved
ClobazamThe serum concentration of Clobazam can be increased when it is combined with Daclatasvir.Approved, Illicit
ClomifeneThe serum concentration of Clomifene can be increased when it is combined with Daclatasvir.Approved, Investigational
ClonidineThe serum concentration of Clonidine can be increased when it is combined with Daclatasvir.Approved
ClopidogrelThe serum concentration of Clopidogrel can be increased when it is combined with Daclatasvir.Approved, Nutraceutical
ClotrimazoleThe metabolism of Daclatasvir can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe serum concentration of Clozapine can be increased when it is combined with Daclatasvir.Approved
CobicistatThe serum concentration of Daclatasvir can be increased when it is combined with Cobicistat.Approved
CobimetinibThe serum concentration of Cobimetinib can be increased when it is combined with Daclatasvir.Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Daclatasvir.Approved
ConivaptanThe serum concentration of Daclatasvir can be increased when it is combined with Conivaptan.Approved, Investigational
Conjugated estrogensThe serum concentration of Conjugated Equine Estrogens can be increased when it is combined with Daclatasvir.Approved
CrizotinibThe metabolism of Daclatasvir can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Daclatasvir can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Daclatasvir.Approved
DabrafenibThe serum concentration of Daclatasvir can be decreased when it is combined with Dabrafenib.Approved
DactinomycinThe serum concentration of Dactinomycin can be increased when it is combined with Daclatasvir.Approved
DapagliflozinThe serum concentration of Dapagliflozin can be increased when it is combined with Daclatasvir.Approved
DarunavirThe serum concentration of Daclatasvir can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Daclatasvir can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Daunorubicin can be increased when it is combined with Daclatasvir.Approved
DebrisoquinThe serum concentration of Debrisoquin can be increased when it is combined with Daclatasvir.Approved
DeferasiroxThe serum concentration of Daclatasvir can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Daclatasvir can be decreased when combined with Delavirdine.Approved
DexamethasoneThe serum concentration of Daclatasvir can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DiazepamThe serum concentration of Diazepam can be increased when it is combined with Daclatasvir.Approved, Illicit, Vet Approved
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be increased when it is combined with Daclatasvir.Approved
DigitoxinThe serum concentration of Digitoxin can be increased when it is combined with Daclatasvir.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Daclatasvir.Approved
DihydroergotamineThe metabolism of Daclatasvir can be decreased when combined with Dihydroergotamine.Approved
DihydrotestosteroneThe serum concentration of Dihydrotestosterone can be increased when it is combined with Daclatasvir.Illicit
DiltiazemThe metabolism of Daclatasvir can be decreased when combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Dipyridamole can be increased when it is combined with Daclatasvir.Approved
DocetaxelThe serum concentration of Docetaxel can be increased when it is combined with Daclatasvir.Approved, Investigational
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Daclatasvir.Approved, Investigational, Vet Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Daclatasvir.Approved, Investigational
DoxycyclineThe metabolism of Daclatasvir can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Daclatasvir can be decreased when combined with Dronedarone.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Daclatasvir.Approved
EfavirenzThe serum concentration of Daclatasvir can be decreased when it is combined with Efavirenz.Approved, Investigational
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Daclatasvir.Approved, Investigational
EnzalutamideThe serum concentration of Daclatasvir can be decreased when it is combined with Enzalutamide.Approved
EpinastineThe serum concentration of Epinastine can be increased when it is combined with Daclatasvir.Approved, Investigational
ErlotinibThe serum concentration of Erlotinib can be increased when it is combined with Daclatasvir.Approved, Investigational
ErythromycinThe metabolism of Daclatasvir can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Daclatasvir can be decreased when it is combined with Eslicarbazepine acetate.Approved
EstradiolThe serum concentration of Estradiol can be increased when it is combined with Daclatasvir.Approved, Investigational, Vet Approved
EstriolThe serum concentration of Estriol can be increased when it is combined with Daclatasvir.Approved, Vet Approved
EstroneThe serum concentration of Estrone can be increased when it is combined with Daclatasvir.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be increased when it is combined with Daclatasvir.Approved
EtoposideThe serum concentration of Etoposide can be increased when it is combined with Daclatasvir.Approved
EtravirineThe serum concentration of Daclatasvir can be decreased when it is combined with Etravirine.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Daclatasvir.Approved
EzetimibeThe serum concentration of Ezetimibe can be increased when it is combined with Daclatasvir.Approved
FesoterodineThe serum concentration of Fesoterodine can be increased when it is combined with Daclatasvir.Approved
FexofenadineThe serum concentration of Fexofenadine can be increased when it is combined with Daclatasvir.Approved
FidaxomicinThe serum concentration of Fidaxomicin can be increased when it is combined with Daclatasvir.Approved
FluconazoleThe metabolism of Daclatasvir can be decreased when combined with Fluconazole.Approved
Fluticasone furoateThe serum concentration of Fluticasone furoate can be increased when it is combined with Daclatasvir.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Daclatasvir.Approved
FluvoxamineThe metabolism of Daclatasvir can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Daclatasvir can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Daclatasvir can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Daclatasvir can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Daclatasvir can be increased when it is combined with Fusidic Acid.Approved
GefitinibThe serum concentration of Gefitinib can be increased when it is combined with Daclatasvir.Approved, Investigational
GemcitabineThe serum concentration of Gemcitabine can be increased when it is combined with Daclatasvir.Approved
GrazoprevirThe serum concentration of Grazoprevir can be increased when it is combined with Daclatasvir.Approved
GrepafloxacinThe serum concentration of Grepafloxacin can be increased when it is combined with Daclatasvir.Withdrawn
HaloperidolThe serum concentration of Haloperidol can be increased when it is combined with Daclatasvir.Approved
HydrocortisoneThe serum concentration of Hydrocortisone can be increased when it is combined with Daclatasvir.Approved, Vet Approved
IbuprofenThe serum concentration of Ibuprofen can be increased when it is combined with Daclatasvir.Approved
IdelalisibThe serum concentration of Daclatasvir can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Daclatasvir can be decreased when combined with Imatinib.Approved
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Daclatasvir.Approved
IndacaterolThe serum concentration of Indacaterol can be increased when it is combined with Daclatasvir.Approved
IndinavirThe serum concentration of Daclatasvir can be increased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Indomethacin can be increased when it is combined with Daclatasvir.Approved, Investigational
IrinotecanThe serum concentration of Irinotecan can be increased when it is combined with Daclatasvir.Approved, Investigational
IsavuconazoniumThe metabolism of Daclatasvir can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Daclatasvir can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Daclatasvir can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Daclatasvir can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Ivermectin can be increased when it is combined with Daclatasvir.Approved, Vet Approved
KetazolamThe serum concentration of Ketazolam can be increased when it is combined with Daclatasvir.Approved
KetoconazoleThe serum concentration of Daclatasvir can be increased when it is combined with Ketoconazole.Approved, Investigational
LamivudineThe serum concentration of Lamivudine can be increased when it is combined with Daclatasvir.Approved, Investigational
LamotrigineThe serum concentration of Lamotrigine can be increased when it is combined with Daclatasvir.Approved, Investigational
LansoprazoleThe serum concentration of Lansoprazole can be increased when it is combined with Daclatasvir.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Daclatasvir.Approved
LenalidomideThe serum concentration of Lenalidomide can be increased when it is combined with Daclatasvir.Approved
LenvatinibThe serum concentration of Lenvatinib can be increased when it is combined with Daclatasvir.Approved
LevetiracetamThe serum concentration of Levetiracetam can be increased when it is combined with Daclatasvir.Approved, Investigational
LevofloxacinThe serum concentration of Levofloxacin can be increased when it is combined with Daclatasvir.Approved, Investigational
LevomilnacipranThe serum concentration of Levomilnacipran can be increased when it is combined with Daclatasvir.Approved
LinagliptinThe serum concentration of Linagliptin can be increased when it is combined with Daclatasvir.Approved
LoperamideThe serum concentration of Loperamide can be increased when it is combined with Daclatasvir.Approved
LopinavirThe serum concentration of Daclatasvir can be increased when it is combined with Lopinavir.Approved
LosartanThe serum concentration of Losartan can be increased when it is combined with Daclatasvir.Approved
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Daclatasvir.Approved, Investigational
LuliconazoleThe serum concentration of Daclatasvir can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Daclatasvir can be decreased when it is combined with Lumacaftor.Approved
MannitolThe serum concentration of Mannitol can be increased when it is combined with Daclatasvir.Approved, Investigational
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Daclatasvir.Approved
MethylprednisoloneThe serum concentration of Methylprednisolone can be increased when it is combined with Daclatasvir.Approved, Vet Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Daclatasvir.Approved, Investigational
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Daclatasvir.Experimental
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Daclatasvir.Approved, Illicit
MifepristoneThe serum concentration of Daclatasvir can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe serum concentration of Mirabegron can be increased when it is combined with Daclatasvir.Approved
MitotaneThe serum concentration of Daclatasvir can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Mitoxantrone can be increased when it is combined with Daclatasvir.Approved, Investigational
ModafinilThe serum concentration of Daclatasvir can be decreased when it is combined with Modafinil.Approved, Investigational
MorphineThe serum concentration of Morphine can be increased when it is combined with Daclatasvir.Approved, Investigational
Mycophenolate mofetilThe serum concentration of Mycophenolate mofetil can be increased when it is combined with Daclatasvir.Approved, Investigational
NadololThe serum concentration of Nadolol can be increased when it is combined with Daclatasvir.Approved
NafcillinThe serum concentration of Daclatasvir can be decreased when it is combined with Nafcillin.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Daclatasvir.Approved
NaloxoneThe serum concentration of Naloxone can be increased when it is combined with Daclatasvir.Approved, Vet Approved
NefazodoneThe serum concentration of Daclatasvir can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Daclatasvir can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Daclatasvir can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Daclatasvir can be decreased when it is combined with Nevirapine.Approved
NicardipineThe serum concentration of Nicardipine can be increased when it is combined with Daclatasvir.Approved
NifedipineThe serum concentration of Nifedipine can be increased when it is combined with Daclatasvir.Approved
NilotinibThe metabolism of Daclatasvir can be decreased when combined with Nilotinib.Approved, Investigational
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Daclatasvir.Approved
NizatidineThe serum concentration of Nizatidine can be increased when it is combined with Daclatasvir.Approved
OlanzapineThe serum concentration of Olanzapine can be increased when it is combined with Daclatasvir.Approved, Investigational
OlaparibThe metabolism of Daclatasvir can be decreased when combined with Olaparib.Approved
OmbitasvirThe serum concentration of Ombitasvir can be increased when it is combined with Daclatasvir.Approved
OsimertinibThe serum concentration of Daclatasvir can be increased when it is combined with Osimertinib.Approved
PaclitaxelThe serum concentration of Paclitaxel can be increased when it is combined with Daclatasvir.Approved, Vet Approved
PalbociclibThe serum concentration of Daclatasvir can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Panobinostat can be increased when it is combined with Daclatasvir.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Daclatasvir.Approved
PentobarbitalThe serum concentration of Daclatasvir can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe serum concentration of Daclatasvir can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Daclatasvir can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Daclatasvir.Approved
PomalidomideThe serum concentration of Pomalidomide can be increased when it is combined with Daclatasvir.Approved
PonatinibThe serum concentration of Ponatinib can be increased when it is combined with Daclatasvir.Approved
PosaconazoleThe serum concentration of Daclatasvir can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Daclatasvir.Approved
PrazosinThe serum concentration of Prazosin can be increased when it is combined with Daclatasvir.Approved
PrednisoloneThe serum concentration of Prednisolone can be increased when it is combined with Daclatasvir.Approved, Vet Approved
PrednisoneThe serum concentration of Prednisone can be increased when it is combined with Daclatasvir.Approved, Vet Approved
PrimidoneThe serum concentration of Daclatasvir can be decreased when it is combined with Primidone.Approved, Vet Approved
ProgesteroneThe serum concentration of Progesterone can be increased when it is combined with Daclatasvir.Approved, Vet Approved
PropranololThe serum concentration of Propranolol can be increased when it is combined with Daclatasvir.Approved, Investigational
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Daclatasvir.Approved
QuetiapineThe serum concentration of Quetiapine can be increased when it is combined with Daclatasvir.Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Daclatasvir.Approved
QuinineThe serum concentration of Quinine can be increased when it is combined with Daclatasvir.Approved
RanitidineThe serum concentration of Ranitidine can be increased when it is combined with Daclatasvir.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Daclatasvir.Approved, Investigational
ReserpineThe serum concentration of Reserpine can be increased when it is combined with Daclatasvir.Approved
RifabutinThe serum concentration of Daclatasvir can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Daclatasvir can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Daclatasvir can be decreased when it is combined with Rifapentine.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Daclatasvir.Approved, Investigational
RisperidoneThe serum concentration of Risperidone can be increased when it is combined with Daclatasvir.Approved, Investigational
RitonavirThe serum concentration of Daclatasvir can be increased when it is combined with Ritonavir.Approved, Investigational
RivaroxabanThe serum concentration of Rivaroxaban can be increased when it is combined with Daclatasvir.Approved
RomidepsinThe serum concentration of Romidepsin can be increased when it is combined with Daclatasvir.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Daclatasvir.Approved
Salicylic acidThe serum concentration of Salicylic acid can be increased when it is combined with Daclatasvir.Approved, Vet Approved
SaquinavirThe serum concentration of Daclatasvir can be increased when it is combined with Saquinavir.Approved, Investigational
SelexipagThe serum concentration of Selexipag can be increased when it is combined with Daclatasvir.Approved
SildenafilThe metabolism of Daclatasvir can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Daclatasvir.Approved
SiltuximabThe serum concentration of Daclatasvir can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Daclatasvir can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Daclatasvir.Approved
SitagliptinThe serum concentration of Sitagliptin can be increased when it is combined with Daclatasvir.Approved, Investigational
SofosbuvirThe serum concentration of Sofosbuvir can be increased when it is combined with Daclatasvir.Approved
SorafenibThe serum concentration of Sorafenib can be increased when it is combined with Daclatasvir.Approved, Investigational
SparfloxacinThe serum concentration of Sparfloxacin can be increased when it is combined with Daclatasvir.Approved
SphingosineThe serum concentration of Sphingosine can be increased when it is combined with Daclatasvir.Experimental
St. John's WortThe serum concentration of Daclatasvir can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Daclatasvir can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Daclatasvir can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Daclatasvir.Approved, Investigational
TamoxifenThe serum concentration of Tamoxifen can be increased when it is combined with Daclatasvir.Approved
Taurocholic AcidThe serum concentration of Taurocholic Acid can be increased when it is combined with Daclatasvir.Experimental
Technetium Tc-99m sestamibiThe serum concentration of Technetium Tc-99m sestamibi can be increased when it is combined with Daclatasvir.Approved
TelaprevirThe serum concentration of Daclatasvir can be increased when it is combined with Telaprevir.Withdrawn
TelithromycinThe serum concentration of Daclatasvir can be increased when it is combined with Telithromycin.Approved
TemsirolimusThe serum concentration of Temsirolimus can be increased when it is combined with Daclatasvir.Approved
TicagrelorThe serum concentration of Ticagrelor can be increased when it is combined with Daclatasvir.Approved
TiclopidineThe metabolism of Daclatasvir can be decreased when combined with Ticlopidine.Approved
TimololThe serum concentration of Timolol can be increased when it is combined with Daclatasvir.Approved
TocilizumabThe serum concentration of Daclatasvir can be decreased when it is combined with Tocilizumab.Approved
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Daclatasvir.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Daclatasvir.Approved, Investigational
ToremifeneThe serum concentration of Toremifene can be increased when it is combined with Daclatasvir.Approved, Investigational
Trastuzumab emtansineThe serum concentration of Trastuzumab emtansine can be increased when it is combined with Daclatasvir.Approved
UbidecarenoneThe serum concentration of Coenzyme Q10 can be increased when it is combined with Daclatasvir.Experimental
UlipristalThe serum concentration of Ulipristal can be increased when it is combined with Daclatasvir.Approved
UmeclidiniumThe serum concentration of Umeclidinium can be increased when it is combined with Daclatasvir.Approved
VecuroniumThe serum concentration of Vecuronium can be increased when it is combined with Daclatasvir.Approved
VenetoclaxThe serum concentration of Venetoclax can be increased when it is combined with Daclatasvir.Approved
VenlafaxineThe metabolism of Daclatasvir can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Daclatasvir can be decreased when combined with Verapamil.Approved
VinblastineThe serum concentration of Vinblastine can be increased when it is combined with Daclatasvir.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Daclatasvir.Approved, Investigational
VismodegibThe serum concentration of Vismodegib can be increased when it is combined with Daclatasvir.Approved
VoriconazoleThe serum concentration of Daclatasvir can be increased when it is combined with Voriconazole.Approved, Investigational
ZidovudineThe serum concentration of Zidovudine can be increased when it is combined with Daclatasvir.Approved
ZiprasidoneThe metabolism of Daclatasvir can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Belema M, Nguyen VN, Bachand C, Deon DH, Goodrich JT, James CA, Lavoie R, Lopez OD, Martel A, Romine JL, Ruediger EH, Snyder LB, St Laurent DR, Yang F, Zhu J, Wong HS, Langley DR, Adams SP, Cantor GH, Chimalakonda A, Fura A, Johnson BM, Knipe JO, Parker DD, Santone KS, Fridell RA, Lemm JA, O'Boyle DR 2nd, Colonno RJ, Gao M, Meanwell NA, Hamann LG: Hepatitis C virus NS5A replication complex inhibitors: the discovery of daclatasvir. J Med Chem. 2014 Mar 13;57(5):2013-32. doi: 10.1021/jm401836p. Epub 2014 Feb 12. [PubMed:24521299 ]
  2. Guedj J, Dahari H, Rong L, Sansone ND, Nettles RE, Cotler SJ, Layden TJ, Uprichard SL, Perelson AS: Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3991-6. doi: 10.1073/pnas.1203110110. Epub 2013 Feb 19. [PubMed:23431163 ]
  3. Lee C: Daclatasvir: potential role in hepatitis C. Drug Des Devel Ther. 2013 Oct 16;7:1223-33. doi: 10.2147/DDDT.S40310. eCollection 2013. [PubMed:24204123 ]
  4. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
  5. Berger C, Romero-Brey I, Radujkovic D, Terreux R, Zayas M, Paul D, Harak C, Hoppe S, Gao M, Penin F, Lohmann V, Bartenschlager R: Daclatasvir-like inhibitors of NS5A block early biogenesis of hepatitis C virus-induced membranous replication factories, independent of RNA replication. Gastroenterology. 2014 Nov;147(5):1094-105.e25. doi: 10.1053/j.gastro.2014.07.019. Epub 2014 Jul 18. [PubMed:25046163 ]
  6. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [PubMed:25585348 ]
  7. Li W, Zhao W, Liu X, Huang X, Lopez OD, Leet JE, Fancher RM, Nguyen V, Goodrich J, Easter J, Hong Y, Caceres-Cortes J, Chang SY, Ma L, Belema M, Hamann LG, Gao M, Zhu M, Shu YZ, Humphreys WG, Johnson BM: Biotransformation of Daclatasvir In Vitro and in Nonclinical Species: Formation of the Main Metabolite by Pyrrolidine delta-Oxidation and Rearrangement. Drug Metab Dispos. 2016 Jun;44(6):809-20. doi: 10.1124/dmd.115.068866. Epub 2016 Mar 30. [PubMed:27029743 ]
  8. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
  9. American Liver Foundation: Advances in Medications to Treat Hepatitis C [Link]
External Links
ATC CodesJ05AX14 — Daclatasvir
AHFS Codes
  • 8:18.40.24
PDB EntriesNot Available
FDA labelDownload (794 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionChronic Hepatitis C Virus (HCV) Infection1
1CompletedNot AvailableChronic Hepatitis C Infection3
1CompletedNot AvailableChronic Hepatitis C Infection / Diabetes Mellitus (DM) / Insulin Resistance1
1CompletedNot AvailableChronic Hepatitis C Infection / HIV Disease1
1CompletedNot AvailableChronic Hepatitis C Virus (HCV) Infection1
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableHepatic Insufficiency1
1CompletedBasic ScienceHepatitis C Infection1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentChronic Hepatitis C Infection1
1, 2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2Active Not RecruitingTreatmentHepatitis C, Chronic1
2CompletedDiagnosticHCV-HIV Co-Infection1
2CompletedTreatmentCHC / Chronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection / HCV1
2CompletedTreatmentChronic Hepatitis C Infection3
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection4
2CompletedTreatmentHIV-HCV1
2CompletedTreatmentHepatitis C Infection4
2CompletedTreatmentHepatitis C Virus (HCV)5
2CompletedTreatmentHepatitis C Virus (HCV) / Hepatitis C Virus Infection1
2CompletedTreatmentHepatitis C Virus Genotype 4 Infection1
2CompletedTreatmentHepatitis C, Chronic2
2TerminatedTreatmentChronic Hepatitis C Infection1
2WithdrawnTreatmentChronic Hepatitis C Infection2
2WithdrawnTreatmentEnd-Stage Renal Disease (ESRD) / Impaired Renal Function1
2WithdrawnTreatmentHepatitis C Virus (HCV)1
2WithdrawnTreatmentHepatitis C Virus Genotype 4 Infection1
2, 3RecruitingTreatmentChronic Hepatitis C Infection1
2, 3RecruitingTreatmentChronic Hepatitis C Infection / HBV Coinfection / Hepatitis B Reactivation1
3CompletedBasic ScienceChronic Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentChronic Hepatitis C Infection14
3CompletedTreatmentChronic Hepatitis C Infection / Liver Cirrhosis1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Genotype 3 Hepatitis C Virus / Hepatitis C Virus (HCV)1
3CompletedTreatmentHepatitis C Virus (HCV)4
3CompletedTreatmentHepatitis C Virus Infection2
3CompletedTreatmentHepatitis C, Genotype 11
3Enrolling by InvitationTreatmentHepatitis C Genotype 41
3Not Yet RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
3RecruitingTreatmentChronic Hepatitis C Infection2
3RecruitingTreatmentHepatitis C, Chronic / Hepatocellular,Carcinoma1
3WithdrawnTreatmentChronic Hepatitis C Infection1
4Active Not RecruitingTreatmentChronic Hepatitis C Infection / Liver Cirrhosis1
4CompletedTreatmentHepatitis C, Chronic1
4RecruitingTreatmentChronic Hepatitis C Infection2
4RecruitingTreatmentChronic Renal Failure (CRF) / Hepatitis C, Chronic1
4WithdrawnTreatmentHepatitis C, Chronic1
Not AvailableActive Not RecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableCompletedNot AvailableChronic Hepatitis C (Disorder)1
Not AvailableEnrolling by InvitationNot AvailableChronic Hepatitis C Infection1
Not AvailableNo Longer AvailableNot AvailableChronic Hepatitis C Virus (HCV) Infection2
Not AvailableNot Yet RecruitingNot AvailableChronic Hepatitis C Infection4
Not AvailableNot Yet RecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Infection1
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1
Not AvailableRecruitingScreeningHepatitis C, Chronic1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral30 mg
TabletOral30 mg/1
TabletOral60 mg/1
TabletOral60 mg
TabletOral90 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8900566 No2007-08-082027-08-08Us
US8642025 No2007-08-112027-08-11Us
US8629171 No2011-06-132031-06-13Us
US8329159 No2008-04-132028-04-13Us
US9421192 No2007-08-082027-08-08Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityFreely soluble (>700 mg/mL)FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00852 mg/mLALOGPS
logP4.67ALOGPS
logP4.18ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)11.15ChemAxon
pKa (Strongest Basic)6.09ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area174.64 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity201.82 m3·mol-1ChemAxon
Polarizability83.91 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resulting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentValine and derivatives
Alternative ParentsBiphenyls and derivatives / Alpha amino acid amides / Phenylimidazoles / N-acylpyrrolidines / Tertiary carboxylic acid amides / Methylcarbamates / Heteroaromatic compounds / Azacyclic compounds / Organonitrogen compounds / Organic oxides
SubstituentsValine or derivatives / Alpha-amino acid amide / Biphenyl / 5-phenylimidazole / 4-phenylimidazole / N-acylpyrrolidine / Monocyclic benzene moiety / Benzenoid / Methylcarbamate / Azole
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorscarbamate ester, imidazoles, biphenyls, carboxamide, valine derivative (CHEBI:82977 )

Targets

1. Nonstructural Protein 5A (NS5A)
Kind
Protein
Organism
Hepatitis C Virus (HCV)
Pharmacological action
unknown
Actions
inhibitor
References
  1. Gao M: Antiviral activity and resistance of HCV NS5A replication complex inhibitors. Curr Opin Virol. 2013 Oct;3(5):514-20. doi: 10.1016/j.coviro.2013.06.014. Epub 2013 Jul 27. [PubMed:23896281 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Uniprot Name:
Cytochrome P450 3A5
Molecular Weight:
57108.065 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Monooxygenase activity
Specific Function:
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name:
CYP3A43
Uniprot ID:
Q9HB55
Uniprot Name:
Cytochrome P450 3A43
Molecular Weight:
57669.21 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Uniprot Name:
Cytochrome P450 3A7
Molecular Weight:
57525.03 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Uniprot Name:
Multidrug resistance protein 1
Molecular Weight:
141477.255 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Uniprot Name:
Solute carrier organic anion transporter family member 1B1
Molecular Weight:
76447.99 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Uniprot Name:
Solute carrier organic anion transporter family member 1B3
Molecular Weight:
77402.175 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Uniprot Name:
ATP-binding cassette sub-family G member 2
Molecular Weight:
72313.47 Da
References
  1. Smith MA, Regal RE, Mohammad RA: Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection. Ann Pharmacother. 2016 Jan;50(1):39-46. doi: 10.1177/1060028015610342. Epub 2015 Oct 20. [PubMed:26486762 ]
Drug created on September 16, 2015 15:59 / Updated on August 08, 2017 11:11