Identification

Name
Simeprevir
Accession Number
DB06290
Type
Small Molecule
Groups
Approved
Description

Simeprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated in patient's with HCV genotype 1 for the treatment of chronic hepatitis C virus (HCV) infection. 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 [7]. Like all NS3/4A inhibitors, simeprevir is a serine protease inhibitor in similarity to Boceprevir and Telaprevir but is classified as a second generation protease inhibitor. This class of antiviral drugs were the first direct acting antivirals approved but are associated with lower cure rates than newer drugs. Broad use of simeprevir occurred when it was used in combination with a newer drug, Sofosbuvir. Inhibiting HCV NS3/4A protease in a potent and highly specific manner, simeprevir is a direct-acting antiviral agent against the hepatitis C virus. Since the viral protease NS3/4A complex is essential for cleaving the HCV encoded polyprotein into individual viral proteins facilitating replication [4], the drug blocks the viral replication process. It is shown to display synergistic effects with interferon-α and HCV NS5B inhibitor, and additive effects with ribavirin in HCV replicon cells [2]. Unlike first generation serine protease inhibitors, simprevir has a sightly different resistance profile where limited therapeutic efficacy of the drug is observed with NS3 Q80K polymorphic variants and simeprevir-specific amino acid position of 168 also results in higher treatment failure rates [3]. The observed prevalence of the N3 Q80K polymorphism was 30% in subjects infected with HCV genotype 1a and 0.5% in subjects infected with HCV genotype 1b [3].

According to 2017 American Association for the Study of Liver Diseases (AASLD) and 2015 consensus guidelines from the Canadian Association for the Study of the Liver (CASL), simeprevir can be used as first-line or second-line threapies for treatment-naïve patients as adjunct to sofosbuvir treatment for genotype 1 or PEG-Interferon/ribavirin combination therapy for genotype 1 or 4. The combination therapy of simeprevir and other antiviral agents are initiated in HCV-positive patients with the intent to cure, or achieve a sustained virologic response (SVR), 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].

Simeprevir was approved by the FDA in November 2014 and is marketed under the brand name Olysio as oral tablets. Administered once daily with food, 150mg simeprevir capsule is used in combination with Sofosbuvir in patients with HCV genotype 1 without cirrhosis for 12 week duration. In patients with HCV genotype 1 with compensated cirrhosis, the treatment is directed for 24 week duration. Sustained virologic response 12 weeks after planned end of treatment (SVR12) was achieved in 170/176 (97%) subjects without cirrhosis treated with 12 weeks simeprevir in combination with sofosbuvir (FDA Label). The overall SVR12 was 88% (44/50) in treatment-naïve patients with cirrhosis [7].

Simeprevir is also used in treatment of HCV genotype 4 patients with or without cirrhosis and is taken with Peginterferon alfa-2a and Ribavirin; this triple therapy allows shortening treatment duration from 48 weeks or longer to 12 or 24 weeks [3] depending on prior response status and presence of HIV-1 co-infection. Prior to initiation of treatment with Peginterferon alfa-2a and Ribavirin, screening for the presence of virus with the NS3 Q80K polymorphism is strongly recommended and if detected, alternative treatment should be considered instead to prevent therapeutic failure. The SVR12 was 83% (29/35) in treatment-naïve patients and 86% (19/22) in relapsing patients.

Structure
Thumb
Synonyms
Not Available
External IDs
TMC 435 / TMC 435350 / TMC-435 / TMC-435350 / TMC435
Product Ingredients
IngredientUNIICASInChI Key
Simeprevir sodium16U7H601841241946-89-3LLXQGDWGCCKOQP-OBABASCOSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GalexosCapsule150 mgOralJanssen Pharmaceuticals2013-11-25Not applicableCanada
OlysioCapsule150 mg/1OralJanssen, Lp2013-11-222018-05-25Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
OlysioSimeprevir (150 mg)CapsuleOralJanssen Cilag International Nv2014-05-142018-05-23Eu
OlysioSimeprevir (150 mg)CapsuleOralJanssen Cilag International Nv2014-05-142018-05-23Eu
Categories
UNII
9WS5RD66HZ
CAS number
923604-59-5
Weight
Average: 749.939
Monoisotopic: 749.291690263
Chemical Formula
C38H47N5O7S2
InChI Key
JTZZSQYMACOLNN-VDWJNHBNSA-N
InChI
InChI=1S/C38H47N5O7S2/c1-21(2)30-20-51-35(40-30)29-18-32(26-13-14-31(49-5)22(3)33(26)39-29)50-24-16-27-28(17-24)36(45)43(4)15-9-7-6-8-10-23-19-38(23,41-34(27)44)37(46)42-52(47,48)25-11-12-25/h8,10,13-14,18,20-21,23-25,27-28H,6-7,9,11-12,15-17,19H2,1-5H3,(H,41,44)(H,42,46)/b10-8-/t23-,24-,27-,28-,38-/m1/s1
IUPAC Name
(1R,4R,6S,7Z,15R,17R)-N-(cyclopropanesulfonyl)-2-hydroxy-17-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)-13-methyl-14-oxo-3,13-diazatricyclo[13.3.0.0⁴,⁶]octadeca-2,7-diene-4-carboximidic acid
SMILES
[H]\C1=C([H])\[C@]2([H])C[C@]2(N=C(O)[C@]2([H])C[C@]([H])(C[C@@]2([H])C(=O)N(C)CCCC1)OC1=C2C=CC(OC)=C(C)C2=NC(=C1)C1=NC(=CS1)C(C)C)C(O)=NS(=O)(=O)C1CC1

Pharmacology

Indication

Indicated for the treatment of adults with chronic hepatitis C virus (HCV) infection: typically in combination with sofosbuvir in patients with HCV genotype 1 without cirrhosis or with compensated cirrhosis and in combination with peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) in patients with HCV genotype 1 or 4 without cirrhosis or with compensated cirrhosis.

Resistance: Reduced susceptibility to simeprevir was most commonly associated with the viral NS3 Q80K polymorphism. Amino acid substitutions at NS3 positions S122, R155 and/or D168 are also shown to reduce susceptibility to simeprevir in genotype 1a/b patients.

Associated Conditions
Pharmacodynamics

Simeprevir is a direct-acting antiviral agent and inhibitor for HCV NS3/4A protease, which is an important enzyme required for viral replication. Unlike Boceprevir and Telaprevir, simeprevir is a competitive, reversible, macrocyclic, noncovalent inhibitor. The macromolecular cyclic portion of the molecule improves the affnity and selectivity characteristics, which allows rapid association and slow dissociation to the protein target through noncovalent binding [3].

Mechanism of action

Simeprevir is accumulated in the liver after uptake into hepatocytes via OATP1B1/3. NS3/4A heterodimeric complex is composed of the cofactor N4A subunit and N3 subunit which contains the proteolytic site. The NS3/4A protease cleaves the HCV polyprotein downstream of the NS3 site, generating non-structural viral proteins NS3, NS4A, NS4B, NS5A and NS5A and subsequently formation of mature proteins [3, 4]. Simeprevir exerts an inhibitory action on HCV polyprotein cleavage via induced-fit binding to an extended S2 subsite located in the NS3 catalytic site [5]. NS3/4A inhibitors usually depend on few interactions located in the substrate binding groove of the viral serine protease, thus are susceptible to resistance and failed treatment from few critical mutations in these sites. At higher concentration above their antiviral half-maximal effective concentration (EC50), simeprevir and other NS3/4A inhibitors also restore interferon (IFN)-signaling pathways that are thought to be disrupted by NS3/4A protease and recover innate immune processes. NS3/4A protease cleaves two essential adaptor proteins that initiate signaling leading to activation of IFN regulatory factor 3 and IFN-α/β synthesis, which are mitochondrial antiviral-signaling proteins (MAVS otherwise known as IPS-1, VISA, or Cardif) and toll/interleukin-1 receptor (TIR)- domain-containing adaptor-inducing IFN-β (TRIF). Blocking the function of these adaptor proteins results in impaired interferon induction. NS3/4A inhibitors recover the proper IFN-signaling pathways [3, 4].

TargetActionsOrganism
ANS3 protease
inhibitor
Hepatitis C virus
Absorption

The mean absolute bioavailability of simeprevir following a single oral 150 mg dose of simeprevir capsule in fed conditions is 62%. Maximum plasma concentrations (Cmax) are typically achieved between 4 to 6 hours following the oral administration.

Volume of distribution

The volume of distribution for simeprevir has yet to be determined. In animal studies, simeprevir is extensively distributed to gut and liver (liver:blood ratio of 29:1 in rat) tissues.

Protein binding

Simeprevir is extensively (99.9%) bound to plasma proteins, mainly to albumin and to a lesser extent, alpha 1-acid glycoprotein. Increased plasma concentration due to drug-drug interactions is expected when co-administering moderate or strong inhibitors of CYP3A, while the opposite effect is predicted from co-administration of moderate or strong inducers of CYP3A.

Metabolism

Simeprevir undergoes hepatic metabolism. The primary metabolic pathway involves CYP3A system-mediated oxidation. Involvement of CYP2C8 and CYP2C19 cannot be excluded.

Route of elimination

Simeprevir is predominantly eliminated through biliary excretion. In a radioactivity study, 91% of radiolabeled drug was detected in the feces and less than 1% was detected in the urine. From the recovered drug in the feces, the unchanged form of simeprevir accounted for 31% of the total administered dose.

Half life

The elimination half-life of simeprevir following 200mg dose administration is about 41 hours in HCV-positive patients and 10 to 13 hours in individuals without HCV infection.

Clearance

The clearance of simeprevir has yet to be determined.

Toxicity

In a combination therapy with sofosbuvir, most common reported adverse effects is fatigue, headache and nausea. In case of triple therapy with PEG-Interferon Alfa-2A and ribavirin, most common adverse effects included rash (including photosensitivity), pruritus and nausea. Elevations of serum bilirubin may be observed due to inhibition of bilirubin transporters OATP1B1 and MRP2 by simeprevir.

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

Interactions

Drug Interactions
DrugInteraction
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Simeprevir.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Simeprevir.
AbirateroneThe serum concentration of Abiraterone can be increased when it is combined with Simeprevir.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Simeprevir.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Simeprevir.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Simeprevir.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Simeprevir.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Simeprevir.
AdinazolamThe serum concentration of Adinazolam can be increased when it is combined with Simeprevir.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Simeprevir.
Food Interactions
  • Simeprevir should be taken with food.

References

Synthesis Reference

Raboisson P, de Kock H, Rosenquist A, Nilsson M, Salvador-Oden L, Lin TI, Roue N, Ivanov V, Wahling H, Wickstrom K, Hamelink E, Edlund M, Vrang L, Vendeville S, Van de Vreken W, McGowan D, Tahri A, Hu L, Boutton C, Lenz O, Delouvroy F, Pille G, Surleraux D, Wigerinck P, Samuelsson B, Simmen K: Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8. doi: 10.1016/j.bmcl.2008.07.088. Epub 2008 Jul 24.

General References
  1. Raboisson P, de Kock H, Rosenquist A, Nilsson M, Salvador-Oden L, Lin TI, Roue N, Ivanov V, Wahling H, Wickstrom K, Hamelink E, Edlund M, Vrang L, Vendeville S, Van de Vreken W, McGowan D, Tahri A, Hu L, Boutton C, Lenz O, Delouvroy F, Pille G, Surleraux D, Wigerinck P, Samuelsson B, Simmen K: Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8. doi: 10.1016/j.bmcl.2008.07.088. Epub 2008 Jul 24. [PubMed:18678486]
  2. Kanda T, Nakamoto S, Wu S, Yokosuka O: New treatments for genotype 1 chronic hepatitis C - focus on simeprevir. Ther Clin Risk Manag. 2014 May 24;10:387-94. doi: 10.2147/TCRM.S50170. eCollection 2014. [PubMed:24920913]
  3. Izquierdo L, Helle F, Francois C, Castelain S, Duverlie G, Brochot E: Simeprevir for the treatment of hepatitis C virus infection. Pharmgenomics Pers Med. 2014 Aug 14;7:241-9. doi: 10.2147/PGPM.S52715. eCollection 2014. [PubMed:25206310]
  4. Ahmed A, Felmlee DJ: Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals. Viruses. 2015 Dec 18;7(12):6716-29. doi: 10.3390/v7122968. [PubMed:26694454]
  5. Cummings MD, Lindberg J, Lin TI, de Kock H, Lenz O, Lilja E, Fellander S, Baraznenok V, Nystrom S, Nilsson M, Vrang L, Edlund M, Rosenquist A, Samuelsson B, Raboisson P, Simmen K: Induced-fit binding of the macrocyclic noncovalent inhibitor TMC435 to its HCV NS3/NS4A protease target. Angew Chem Int Ed Engl. 2010 Feb 22;49(9):1652-5. doi: 10.1002/anie.200906696. [PubMed:20166108]
  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. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
External Links
KEGG Drug
D10081
PubChem Compound
24873435
PubChem Substance
175427067
ChemSpider
23331536
BindingDB
50336504
ChEBI
134743
ChEMBL
CHEMBL501849
HET
30B
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Simeprevir
ATC Codes
J05AE14 — SimeprevirG01AE10 — Combinations of sulfonamides
AHFS Codes
  • 08:18.40.20 — HCV Protease Inhibitors
PDB Entries
3kee
FDA label
Download (1.31 MB)
MSDS
Download (57.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherHealthy Volunteers2
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection3
1CompletedTreatmentHealthy Male Participants1
1CompletedTreatmentHealthy Participants1
1CompletedTreatmentHealthy Volunteers7
1CompletedTreatmentHepatitis C Viral Infection4
1CompletedTreatmentHepatitis C Viral Infection / Viruses1
1CompletedTreatmentHepatitis C Virus (HCV)12
1TerminatedTreatmentHealthy Volunteers1
2Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedNot AvailableChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentChronic Hepatitis C Virus1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection10
2CompletedTreatmentHepatitis C Viral Infection5
2CompletedTreatmentHepatitis C Virus (HCV)2
2CompletedTreatmentHepatitits C1
2RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2WithdrawnTreatmentEnd-Stage Renal Disease (ESRD) / Impaired Renal Function1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection5
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Genotype 4 Chronic Hepatitis C1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Infection NOS1
3CompletedTreatmentHepatitis C Viral Infection6
3CompletedTreatmentHepatitis C Virus Genotype-11
3CompletedTreatmentHepatitis C Virus Infection2
3RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatocellular,Carcinoma1
4CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection2
4CompletedTreatmentHepatitis C Viral Infection2
4WithdrawnTreatmentChronic Hepatitis C Virus (HCV) Infection / HIV CDC Category A11
4WithdrawnTreatmentPT-NANBH1
Not AvailableCompletedNot AvailableChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableCompletedOtherHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableRecruitingNot AvailableHepatitis C Viral Infection1
Not AvailableRecruitingTreatmentHCV Coinfection1
Not AvailableTerminatedNot AvailableChronic Hepatitis C Virus (HCV) Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral150 mg
CapsuleOral150 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8349869No2006-07-282026-07-28Us
US8148399No2009-09-052029-09-05Us
US8754106No2006-07-282026-07-28Us
US8741926No2006-07-282026-07-28Us
US9040562No2006-07-282026-07-28Us
US7671032No2005-05-192025-05-19Us
US9623022No2006-07-282026-07-28Us
US9353103No2006-07-282026-07-28Us
US9856265No2006-07-282026-07-28Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)225MSDS
water solubilityInsolubleFDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00458 mg/mLALOGPS
logP4.82ALOGPS
logP5.74ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)5.87ChemAxon
pKa (Strongest Basic)1.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area163.87 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity207.79 m3·mol-1ChemAxon
Polarizability80.18 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
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 macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolactams
Sub Class
Not Available
Direct Parent
Macrolactams
Alternative Parents
Alpha amino acid amides / Quinolines and derivatives / Anisoles / 2,4-disubstituted thiazoles / Alkyl aryl ethers / Pyridines and derivatives / Cyclopropanecarboxylic acids and derivatives / Tertiary carboxylic acid amides / Organosulfonic acids and derivatives / Aminosulfonyl compounds
show 9 more
Substituents
Macrolactam / Alpha-amino acid amide / Alpha-amino acid or derivatives / Quinoline / Anisole / 2,4-disubstituted 1,3-thiazole / Alkyl aryl ether / Cyclopropanecarboxylic acid or derivatives / Pyridine / Benzenoid
show 25 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
Not Available
Uniprot ID
Q91RS4
Uniprot Name
NS3 protease
Molecular Weight
19113.77 Da
References
  1. Raboisson P, de Kock H, Rosenquist A, Nilsson M, Salvador-Oden L, Lin TI, Roue N, Ivanov V, Wahling H, Wickstrom K, Hamelink E, Edlund M, Vrang L, Vendeville S, Van de Vreken W, McGowan D, Tahri A, Hu L, Boutton C, Lenz O, Delouvroy F, Pille G, Surleraux D, Wigerinck P, Samuelsson B, Simmen K: Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8. doi: 10.1016/j.bmcl.2008.07.088. Epub 2008 Jul 24. [PubMed:18678486]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
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
References
  1. OLYSIO (simeprevir) capsules - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Intestinal CYP3A4 activity is impacted by Simeprevir but hepatic CYP3A4 activity is not impacted.
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

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Unknown
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
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da

Drug created on March 19, 2008 10:22 / Updated on September 23, 2018 19:37