Identification

Name
Voxilaprevir
Accession Number
DB12026
Type
Small Molecule
Groups
Approved, Investigational
Description

Voxilaprevir is a Direct-Acting Antiviral (DAA) medication used as part of combination therapy to treat chronic Hepatitis C, 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 [3].

Voxilaprevir exerts its antiviral action by reversibley binding and inhibiting the NS3/4A serine protease of Hepatitis C Virus (HCV) [Label]. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B [2]. By inhibiting viral protease NS3/4A, voxilaprevir therefore prevents viral replication and function. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as voxilaprevir.

Voxilaprevir has been available since July 2017 in a fixed dose combination product with Sofosbuvir and Velpatasvir as the commercially available product Vosevi. Vosevi is approved for the treatment of adult patients with chronic HCV infection with genotype 1, 2, 3, 4, 5, or 6 infection [Label]. Notably, Vosevi is approved for use in patients with genotypes 1-6 who have been previously treated with an NS5A inhibitor, or patients with genotypes 1a or 3 infection and have previously been treated with an HCV regimen containing Sofosbuvir without an NS5A inhibitor [4]. Prior to Vosevi, there were no approved retreatment options for patients who have previously received, and failed, a regimen containing an NS5A inhibitor for treatment of chronic HCV infection.

Structure
Thumb
Synonyms
Not Available
External IDs
GS 9857 / GS-9857 / GS9857
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VoseviVoxilaprevir (100 mg/1) + Sofosbuvir (400 mg/1) + Velpatasvir (100 mg/1)Tablet, film coatedOralGilead Sciences2017-07-18Not applicableUs
VoseviVoxilaprevir (100 mg) + Sofosbuvir (400 mg) + Velpatasvir (100 mg)TabletOralGilead Sciences2017-09-18Not applicableCanada
Categories
UNII
0570F37359
CAS number
1535212-07-7
Weight
Average: 868.94
Monoisotopic: 868.345261104
Chemical Formula
C40H52F4N6O9S
InChI Key
MZBLZLWXUBZHSL-FZNJKFJKSA-N
InChI
InChI=1S/C40H52F4N6O9S/c1-7-22-27-19-50(28(22)32(51)48-39(18-23(39)31(41)42)35(53)49-60(55,56)38(5)14-15-38)34(52)30(37(2,3)4)47-36(54)59-26-16-20(26)10-8-9-13-40(43,44)29-33(58-27)46-25-17-21(57-6)11-12-24(25)45-29/h11-12,17,20,22-23,26-28,30-31H,7-10,13-16,18-19H2,1-6H3,(H,47,54)(H,48,51)(H,49,53)/t20-,22-,23+,26-,27+,28+,30-,39-/m1/s1
IUPAC Name
(1R,18R,20R,24S,27S,28S)-24-tert-butyl-N-[(1R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-28-ethyl-13,13-difluoro-7-methoxy-22,25-dioxo-2,21-dioxa-4,11,23,26-tetraazapentacyclo[24.2.1.0^{3,12}.0^{5,10}.0^{18,20}]nonacosa-3(12),4,6,8,10-pentaene-27-carboxamide
SMILES
CC[C@@H]1[C@@H]2CN([C@@H]1C(=O)N[C@@]1(C[C@H]1C(F)F)C(=O)NS(=O)(=O)C1(C)CC1)C(=O)[C@@H](NC(=O)O[C@@H]1C[C@H]1CCCCC(F)(F)C1=C(O2)N=C2C=C(OC)C=CC2=N1)C(C)(C)C

Pharmacology

Indication

Vosevi (Voxilaprevir/Sofosbuvir/Velpatasvir) is approved for use in patients with genotypes 1-6 who have been previously treated with an NS5A inhibitor, or patients with genotypes 1a or 3 infection who have previously been treated with an HCV regimen containing Sofosbuvir without an NS5A inhibitor [4].

Associated Conditions
Pharmacodynamics

Voxilaprevir is a direct-acting antiviral agent that targets viral NS3/4A protein and causes a decrease in serum HCV RNA levels. It disrupts HCV replication by specifically inhibiting the critical functions of NS3/4A protein in the replication complex. It does not appear to prolong the QT interval even when given at 9 times the maximum recommended dose [Label].

Mechanism of action

Voxilaprevir exerts its antiviral action by reversibley binding and inhibiting the NS3/4A serine protease of Hepatitis C Virus (HCV) [Label]. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B [2]. By inhibiting viral protease NS3/4A, voxilaprevir therefore prevents viral replication and function.

TargetActionsOrganism
ANS3/4A protein
inhibitor
Hepatitis C virus
Absorption

When provided as the fixed dose combination product Vosevi with Sofosbuvir and Velpatasvir, voxilaprevir reaches a maximum concentration (Cmax) of 192 ng/mL at a maximum time (Tmax) of 4 hours post-dose [Label].

Volume of distribution
Not Available
Protein binding

Voxilaprevir is more than 99% bound to human plasma proteins [Label].

Metabolism

Voxilaprevir is primarily metabolized by Cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2C8 and CYP1A2[Label].

Route of elimination

Voxilaprevir is primarily eliminated via biliary excretion [Label].

Half life

33 hr [Label]

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Hepatitis C Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Voxilaprevir can be increased when it is combined with Abiraterone.Approved
Acetyl sulfisoxazoleThe metabolism of Voxilaprevir can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Voxilaprevir.Approved
AmiodaroneThe metabolism of Voxilaprevir can be decreased when combined with Amiodarone.Approved, Investigational
ApalutamideThe serum concentration of Voxilaprevir can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Voxilaprevir can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Voxilaprevir can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Voxilaprevir can be decreased when combined with Atomoxetine.Approved
AzithromycinThe metabolism of Voxilaprevir can be decreased when combined with Azithromycin.Approved
BoceprevirThe metabolism of Voxilaprevir can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Voxilaprevir can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Voxilaprevir can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Voxilaprevir.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Voxilaprevir.Approved, Investigational
CaffeineThe metabolism of Voxilaprevir can be decreased when combined with Caffeine.Approved
CarbamazepineThe metabolism of Voxilaprevir can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Voxilaprevir can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Voxilaprevir can be increased when it is combined with Ceritinib.Approved
CitalopramThe metabolism of Voxilaprevir can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Voxilaprevir can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Voxilaprevir can be decreased when combined with Clemastine.Approved, Investigational
ClotrimazoleThe metabolism of Voxilaprevir can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Voxilaprevir can be decreased when combined with Cobicistat.Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Voxilaprevir.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Voxilaprevir.Approved, Investigational
CrisaboroleThe metabolism of Voxilaprevir can be decreased when combined with Crisaborole.Approved, Investigational
CrizotinibThe metabolism of Voxilaprevir can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Voxilaprevir can be decreased when combined with Curcumin.Approved, Investigational
CyclosporineThe metabolism of Voxilaprevir can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Cyproterone acetateThe serum concentration of Voxilaprevir can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Voxilaprevir.Approved
DabrafenibThe serum concentration of Voxilaprevir can be decreased when it is combined with Dabrafenib.Approved, Investigational
DarunavirThe metabolism of Voxilaprevir can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Voxilaprevir can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Voxilaprevir can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Voxilaprevir can be decreased when combined with Delavirdine.Approved
DihydroergotamineThe metabolism of Voxilaprevir can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe metabolism of Voxilaprevir can be decreased when combined with Diltiazem.Approved, Investigational
DosulepinThe metabolism of Voxilaprevir can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Voxilaprevir.Approved, Investigational
DoxycyclineThe metabolism of Voxilaprevir can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Voxilaprevir can be decreased when combined with Dronedarone.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Voxilaprevir.Approved
EfavirenzThe metabolism of Voxilaprevir can be decreased when combined with Efavirenz.Approved, Investigational
EltrombopagThe serum concentration of Voxilaprevir can be increased when it is combined with Eltrombopag.Approved
EnzalutamideThe serum concentration of Voxilaprevir can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Voxilaprevir can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Voxilaprevir.Approved
FelodipineThe metabolism of Voxilaprevir can be decreased when combined with Felodipine.Approved, Investigational
FluconazoleThe metabolism of Voxilaprevir can be decreased when combined with Fluconazole.Approved, Investigational
FluvoxamineThe metabolism of Voxilaprevir can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Voxilaprevir can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Voxilaprevir can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Voxilaprevir can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Voxilaprevir can be increased when it is combined with Fusidic Acid.Approved, Investigational
IdelalisibThe metabolism of Voxilaprevir can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of Voxilaprevir can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Voxilaprevir can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Voxilaprevir can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoleThe serum concentration of Voxilaprevir can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Voxilaprevir can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Voxilaprevir can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe metabolism of Voxilaprevir can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Voxilaprevir can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Voxilaprevir can be decreased when combined with Ketoconazole.Approved, Investigational
LapatinibThe metabolism of Voxilaprevir can be decreased when combined with Lapatinib.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Voxilaprevir.Approved
LidocaineThe metabolism of Voxilaprevir can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Voxilaprevir can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Voxilaprevir can be decreased when combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Voxilaprevir can be increased when it is combined with Lorpiprazole.Approved
LosartanThe metabolism of Voxilaprevir can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Voxilaprevir can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Voxilaprevir can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Voxilaprevir can be increased when it is combined with Lumacaftor.Approved
MexiletineThe metabolism of Voxilaprevir can be decreased when combined with Mexiletine.Approved, Investigational
MidostaurinThe metabolism of Voxilaprevir can be decreased when combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Voxilaprevir can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Voxilaprevir can be decreased when it is combined with Mitotane.Approved
NabiloneThe metabolism of Voxilaprevir can be decreased when combined with Nabilone.Approved, Investigational
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Voxilaprevir.Approved
NefazodoneThe metabolism of Voxilaprevir can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Voxilaprevir can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Voxilaprevir can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Voxilaprevir can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Voxilaprevir can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Voxilaprevir can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Voxilaprevir can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Voxilaprevir can be increased when it is combined with Palbociclib.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Voxilaprevir.Approved
Peginterferon alfa-2bThe serum concentration of Voxilaprevir can be increased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Voxilaprevir can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Voxilaprevir can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of Voxilaprevir can be increased when combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Voxilaprevir can be decreased when combined with Pioglitazone.Approved, Investigational
PitolisantThe serum concentration of Voxilaprevir can be decreased when it is combined with Pitolisant.Approved, Investigational
PosaconazoleThe metabolism of Voxilaprevir can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Voxilaprevir can be increased when combined with Primidone.Approved, Vet Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Voxilaprevir.Approved
QuinineThe metabolism of Voxilaprevir can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Voxilaprevir can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Voxilaprevir.Approved, Investigational
RifabutinThe metabolism of Voxilaprevir can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Voxilaprevir can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Voxilaprevir can be increased when combined with Rifapentine.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Voxilaprevir.Approved, Investigational
RolapitantThe serum concentration of Voxilaprevir can be increased when it is combined with Rolapitant.Approved, Investigational
RopiniroleThe metabolism of Voxilaprevir can be decreased when combined with Ropinirole.Approved, Investigational
RosiglitazoneThe metabolism of Voxilaprevir can be decreased when combined with Rosiglitazone.Approved, Investigational
RucaparibThe metabolism of Voxilaprevir can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe metabolism of Voxilaprevir can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Voxilaprevir can be decreased when used in combination with Sarilumab.Approved, Investigational
SecobarbitalThe metabolism of Voxilaprevir can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Voxilaprevir can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Voxilaprevir.Approved
SiltuximabThe serum concentration of Voxilaprevir can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Voxilaprevir can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Voxilaprevir can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Voxilaprevir can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleThe metabolism of Voxilaprevir can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Voxilaprevir can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TamoxifenThe metabolism of Voxilaprevir can be decreased when combined with Tamoxifen.Approved
TelaprevirThe metabolism of Voxilaprevir can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Voxilaprevir can be decreased when combined with Telithromycin.Approved
Tenofovir disoproxilThe metabolism of Voxilaprevir can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Voxilaprevir can be increased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Voxilaprevir can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Voxilaprevir can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Voxilaprevir can be decreased when it is combined with Tocilizumab.Approved
TopiroxostatThe metabolism of Voxilaprevir can be decreased when combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Voxilaprevir.Approved, Investigational
TrimethoprimThe metabolism of Voxilaprevir can be decreased when combined with Trimethoprim.Approved, Vet Approved
VemurafenibThe serum concentration of Voxilaprevir can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Voxilaprevir can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Voxilaprevir can be decreased when combined with Verapamil.Approved
VincristineThe excretion of Vincristine can be decreased when combined with Voxilaprevir.Approved, Investigational
VoriconazoleThe metabolism of Voxilaprevir can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Voxilaprevir can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Voxilaprevir can be decreased when combined with Zucapsaicin.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Bourliere M, Gordon SC, Flamm SL, Cooper CL, Ramji A, Tong M, Ravendhran N, Vierling JM, Tran TT, Pianko S, Bansal MB, de Ledinghen V, Hyland RH, Stamm LM, Dvory-Sobol H, Svarovskaia E, Zhang J, Huang KC, Subramanian GM, Brainard DM, McHutchison JG, Verna EC, Buggisch P, Landis CS, Younes ZH, Curry MP, Strasser SI, Schiff ER, Reddy KR, Manns MP, Kowdley KV, Zeuzem S: Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017 Jun 1;376(22):2134-2146. doi: 10.1056/NEJMoa1613512. [PubMed:28564569]
  2. Moradpour D, Penin F: Hepatitis C virus proteins: from structure to function. Curr Top Microbiol Immunol. 2013;369:113-42. doi: 10.1007/978-3-642-27340-7_5. [PubMed:23463199]
  3. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
  4. FDA News Release: FDA approves Vosevi for Hepatitis C [Link]
External Links
PubChem Compound
89921642
PubChem Substance
347828341
ChemSpider
44209500
ChEMBL
CHEMBL3707372
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Voxilaprevir
FDA label
Download (1.34 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHCV Infections3
1CompletedTreatmentHepatitis C Virus Infection1
2Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentHepatitis C Virus Infection3
3Active Not RecruitingTreatmentHepatitis C Virus Infection1
3CompletedTreatmentHepatitis C Viral Infection2
3CompletedTreatmentHepatitis C Virus Infection2
4Active Not RecruitingTreatmentHCV Coinfection / Human Immunodeficiency Virus (HIV) / Liver Diseases1
Not AvailableEnrolling by InvitationNot AvailableHepatitis C Virus Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7964580No2009-03-262029-03-26Us
US8334270No2008-03-212028-03-21Us
US8633309No2009-03-262029-03-26Us
US8618076No2010-12-112030-12-11Us
US8735372No2008-03-212028-03-21Us
US8580765No2008-03-212028-03-21Us
US8889159No2009-03-262029-03-26Us
US9085573No2008-03-212028-03-21Us
US9284342No2010-09-132030-09-13Us
US8940718No2012-11-162032-11-16Us
US8575135No2012-11-162032-11-16Us
US8921341No2012-11-162032-11-16Us
US9585906No2008-03-212028-03-21Us
US9296782No2014-07-172034-07-17Us
US9868745No2012-11-162032-11-16Us

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0506 mg/mLALOGPS
logP3.98ALOGPS
logP4.9ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)3.74ChemAxon
pKa (Strongest Basic)-0.84ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area195.22 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity203.02 m3·mol-1ChemAxon
Polarizability85.37 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Cyclic peptides
Alternative Parents
Macrolactams / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Quinoxalines / Pyrrolidinecarboxamides / Anisoles / Alkyl aryl ethers / Pyrazines / Cyclopropanecarboxylic acids and derivatives / Tertiary carboxylic acid amides
show 15 more
Substituents
Cyclic alpha peptide / Macrolactam / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Diazanaphthalene / Alpha-amino acid or derivatives / Quinoxaline / Anisole / Phenol ether / Pyrrolidine carboxylic acid or derivatives
show 34 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Hepatitis C virus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type peptidase activity
Specific Function
Not Available
Gene Name
NS3/4A
Uniprot ID
B0B3C9
Uniprot Name
Genome polyprotein
Molecular Weight
72789.28 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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 fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da

Drug created on October 20, 2016 15:12 / Updated on July 02, 2018 19:31