Identification

Name
Ombitasvir
Accession Number
DB09296
Type
Small Molecule
Groups
Approved
Description

Ombitasvir is a direct acting antiviral 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 [8]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Ombitasvir. Ombitasvir is an inhibitor of NS5A, a protein essential for viral replication and virion assembly [FDA Label]. The barrier for develoment of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAs [5].

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Ombitasvir as a first line therapy option when used in combination with other antivirals for genotypes 1a, 1b, and 4 [8]. Depending on the genotype, Ombitasvir is often used in combination with other antivirals such as Dasabuvir, Paritaprevir, Ritonavir, and Ribavirin 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]. Treatment with direct acting antivirals such as Ombitasvir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [7].

Ombutasvir first came on the market as a fixed-dose combination product with Dasabuvir, Paritaprevir, and Ritonavir as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.

Ombutasvir is also available as a fixed-dose combination product with Paritaprevir and Ritonavir as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

In Canada, Ombutasvir is also available as a fixed-dose combination product with Dasabuvir, Paritaprevir, and Ritonavir as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis.

Structure
Thumb
Synonyms
  • dimethyl ([(2S,5S)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl]bis{(4,1-phenylene)carbamoyl(2S)pyrrolidine-2,1-diyl[(2S)-3-methyl-1-oxobutane-1,2-diyl]})biscarbamate
External IDs
ABT 267 / ABT-267 / ABT267
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Holkira PakOmbitasvir (12.5 mg) + Dasabuvir (250 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg)Kit; TabletOralAbbvie2015-01-06Not applicableCanada
TechnivieOmbitasvir (12.5 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg)TabletOralAbbvie2015-11-24Not applicableCanada
TechnivieOmbitasvir + Paritaprevir + RitonavirKitAbbvie2015-07-24Not applicableUs
Viekira PakOmbitasvir + Dasabuvir + Paritaprevir + RitonavirKitAbbvie2014-12-19Not applicableUs
Viekira XROmbitasvir + Dasabuvir + Paritaprevir + RitonavirKitAbbvie2016-07-22Not applicableUs
Categories
UNII
2302768XJ8
CAS number
1258226-87-7
Weight
Average: 894.127
Monoisotopic: 893.505112145
Chemical Formula
C50H67N7O8
InChI Key
PIDFDZJZLOTZTM-KHVQSSSXSA-N
InChI
InChI=1S/C50H67N7O8/c1-30(2)42(53-48(62)64-8)46(60)55-28-10-12-40(55)44(58)51-35-20-14-32(15-21-35)38-26-27-39(57(38)37-24-18-34(19-25-37)50(5,6)7)33-16-22-36(23-17-33)52-45(59)41-13-11-29-56(41)47(61)43(31(3)4)54-49(63)65-9/h14-25,30-31,38-43H,10-13,26-29H2,1-9H3,(H,51,58)(H,52,59)(H,53,62)(H,54,63)/t38-,39-,40-,41-,42-,43-/m0/s1
IUPAC Name
methyl N-[(2S)-1-[(2S)-2-({4-[(2S,5S)-1-(4-tert-butylphenyl)-5-{4-[(2S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl]pyrrolidine-2-amido]phenyl}pyrrolidin-2-yl]phenyl}carbamoyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
SMILES
COC(=O)N[[email protected]@H](C(C)C)C(=O)N1CCC[[email protected]]1C(=O)NC1=CC=C(C=C1)[[email protected]@H]1CC[[email protected]](N1C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(NC(=O)[[email protected]@H]2CCCN2C(=O)[[email protected]@H](NC(=O)OC)C(C)C)C=C1

Pharmacology

Indication

When used in combination with Paritaprevir and Ritonavir (as the fixed dose product Technivie), Ombitasvir is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis [9].

When used in combination with Paritaprevir, Ritonavir, and Dasabuvir (as the fixed dose product Viekira Pak), Ombitasvir is indicated for the treatment of HCV genotype 1b and ,when combined with Ribavirin, for the treatment of HCV genotype 1a [FDA Label]

Structured Indications
Pharmacodynamics

Ombitasvir is classified as a direct acting antiviral and acts against HCV to inhibit viral replication [FDA Label].

Mechanism of action

Ombitasvir is an inhibitor of the HCV non-structural protein 5A. While the precise role of this protein is unknown, it is essential to viral replication and virion assembly [FDA Label]. Potential modes of action of NS5A inhibitors like Elbasvir include blocking signaling interactions, redistribution of NS5A from the endoplasmic reticulum to the surface of lipid droplets, and modification of the HCV replication complex [5].

TargetActionsOrganism
ANonstructural protein 5A
inhibitor
Hepatitis C virus
Absorption

Ombitasvir reaches peak plasma concentration 5 hours after administration [FDA Label]. It has an absolute bioavailability of 48%. Taking ombitasvir with high or normal fat meals increases exposure by 1.76 or 1.82 fold respectively.

Volume of distribution

Ombitasvir has a volume of distribution at steady state of 173 liters [FDA Label].

Protein binding

Ombitasvir is 99.9% bound to human plasma proteins [FDA Label].

Metabolism

Ombitasvir is mainly metabolized by amide hydrolysis followed by CYP2C8-mediated oxidative metabolism [FDA Label].

Route of elimination

Ombitasvir is mainly excreted in the feces (90.2%) with very little excreted in the urine (1.91%) [FDA Label]. 87.8% and 0.03% of the dose excreted in the feces and urine respectively is present as the parent compound.

Half life

Ombitasvir has a half life of elimination of 21-25 hours [FDA Label]

Clearance

Clearance of Ombitasvir has not been determined.

Toxicity

The most common adverse effects of Viekira Pak either in combination with or without Ribavirin were pruritus, nausea, insomnia, and asthenia [FDA Label]. The most common adverse effects of Technivie with or without Ribavirin were asthenia, fatigue, nausea, insomnia and pruritus [9].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Ombitasvir can be increased when it is combined with Abiraterone.Approved
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Ombitasvir.Approved, Illicit
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Ombitasvir.Approved, Illicit, Investigational
AmiodaroneThe serum concentration of Amiodarone can be increased when it is combined with Ombitasvir.Approved, Investigational
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Ombitasvir.Approved
BuprenorphineThe serum concentration of Buprenorphine can be increased when it is combined with Ombitasvir.Approved, Illicit, Investigational, Vet Approved
CarbamazepineThe metabolism of Ombitasvir can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Ombitasvir can be decreased when combined with Celecoxib.Approved, Investigational
CrisaboroleThe metabolism of Ombitasvir can be decreased when combined with Crisaborole.Approved
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Ombitasvir.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Ombitasvir can be decreased when it is combined with Dabrafenib.Approved
DeferasiroxThe serum concentration of Ombitasvir can be increased when it is combined with Deferasirox.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Ombitasvir.Approved
EfavirenzThe metabolism of Ombitasvir can be decreased when combined with Efavirenz.Approved, Investigational
EltrombopagThe serum concentration of Ombitasvir can be increased when it is combined with Eltrombopag.Approved
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Ombitasvir.Approved, Illicit, Investigational, Vet Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Ombitasvir.Approved
FosphenytoinThe metabolism of Ombitasvir can be increased when combined with Fosphenytoin.Approved
IrbesartanThe metabolism of Ombitasvir can be decreased when combined with Irbesartan.Approved, Investigational
LumacaftorThe serum concentration of Ombitasvir can be increased when it is combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Ombitasvir can be increased when it is combined with Mifepristone.Approved, Investigational
PhenobarbitalThe metabolism of Ombitasvir can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Ombitasvir can be increased when combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Ombitasvir can be decreased when combined with Pioglitazone.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Ombitasvir.Approved
PrimidoneThe metabolism of Ombitasvir can be increased when combined with Primidone.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Ombitasvir.Approved
RabeprazoleThe metabolism of Ombitasvir can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe serum concentration of Ombitasvir can be increased when it is combined with Ranolazine.Approved, Investigational
RifampicinThe metabolism of Ombitasvir can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Ombitasvir can be increased when combined with Rifapentine.Approved
RosiglitazoneThe metabolism of Ombitasvir can be decreased when combined with Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Ombitasvir.Approved
SecobarbitalThe metabolism of Ombitasvir can be increased when combined with Secobarbital.Approved, Vet Approved
SirolimusThe serum concentration of Sirolimus can be increased when it is combined with Ombitasvir.Approved, Investigational
SulfamethoxazoleThe metabolism of Ombitasvir can be decreased when combined with Sulfamethoxazole.Approved
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Ombitasvir.Approved, Investigational
TeriflunomideThe serum concentration of Ombitasvir can be increased when it is combined with Teriflunomide.Approved
TopiroxostatThe metabolism of Ombitasvir can be decreased when combined with Topiroxostat.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Shen J, Serby M, Surber B, Lee AJ, Ma J, Badri P, Menon R, Kavetskaia O, de Morais SM, Sydor J, Fischer V: Metabolism and Disposition of Pan-Genotypic Inhibitor of Hepatitis C Virus NS5A Ombitasvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1148-57. doi: 10.1124/dmd.115.067496. Epub 2016 May 13. [PubMed:27179128]
  2. DeGoey DA, Randolph JT, Liu D, Pratt J, Hutchins C, Donner P, Krueger AC, Matulenko M, Patel S, Motter CE, Nelson L, Keddy R, Tufano M, Caspi DD, Krishnan P, Mistry N, Koev G, Reisch TJ, Mondal R, Pilot-Matias T, Gao Y, Beno DW, Maring CJ, Molla A, Dumas E, Campbell A, Williams L, Collins C, Wagner R, Kati WM: Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014 Mar 13;57(5):2047-57. doi: 10.1021/jm401398x. Epub 2014 Jan 15. [PubMed:24400777]
  3. Keating GM: Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection. Drugs. 2016 Aug;76(12):1203-11. doi: 10.1007/s40265-016-0612-1. [PubMed:27401997]
  4. Macdonald A, Harris M: Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol. 2004 Sep;85(Pt 9):2485-502. [PubMed:15302943]
  5. Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [PubMed:28497432]
  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. Dusheiko G: Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):112S-121S. [PubMed:9305675]
  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. Dailymed: Technivie [Link]
External Links
KEGG Drug
D10745
PubChem Compound
54767916
PubChem Substance
310265188
ChemSpider
31136214
ChEBI
85183
ChEMBL
CHEMBL3127326
PharmGKB
PA166163409
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ombitasvir
ATC Codes
J05AX67 — Ombitasvir, paritaprevir and ritonavirJ05AX66 — Dasabuvir, ombitasvir, paritaprevir and ritonavir
FDA label
Download (540 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAbsolute Bioavailability1
1CompletedTreatmentHCV Infections1
1CompletedTreatmentHealthy Volunteers1
2Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 11
2CompletedTreatmentChronic Hepatitis C Infection3
2CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 11
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 1a1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated liver disease / Hepatitis C Virus (HCV)1
2CompletedTreatmentChronic Hepatitis C Virus Infection1
2CompletedTreatmentHepatitis C Virus (HCV)1
2CompletedTreatmentHepatitis C, Chronic1
2RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3RecruitingTreatmentChronic Hepatitis C Infection / HBV Coinfection / Hepatitis B Reactivation1
3Active Not RecruitingTreatmentChronic Hepatitis C Genotype 12
3Active Not RecruitingTreatmentHepatitis C, Acute1
3CompletedOtherChronic Hepatitis C Infection1
3CompletedTreatmentChronic Hepatitis C Infection10
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentChronic Hepatitis C Infection / Chronic Kidney Disease (CKD) / Genotype 1a / Genotype 4 / HCV / IFN / PegIFN1
3CompletedTreatmentChronic Hepatitis C Infection / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Infection / Compensated liver disease / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Virus1
3CompletedTreatmentChronic Hepatitis C Virus (HCV Infection Genotype 1)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Cirrhosis, Decompensated / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated Cirrhosis and Non-cirrhotics / Hepatitis C Virus Infection / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Compensated liver disease / End-Stage Renal Disease (ESRD) / Hepatitis C Virus (HCV) / Severe Renal Impairment1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C (HCV) / Hepatitis C Genotype 1a1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C Virus (HCV) / Liver Cirrhosis1
3CompletedTreatmentChronic Hepatitis C Virus / Hepatitis C Virus (HCV)2
3CompletedTreatmentHepatitis C Infection / Hepatitis C Virus (HCV)1
3CompletedTreatmentHepatitis C Virus (HCV)2
3RecruitingTreatmentChronic Hepatitis C Infection1
3WithdrawnTreatmentChronic Hepatitis C Virus1
4Active Not RecruitingTreatmentHepatitis C Virus (HCV)1
4Active Not RecruitingTreatmentHepatitis C, Chronic1
4Not Yet RecruitingTreatmentAntiviral Drug Adverse Reaction1
4RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
4RecruitingTreatmentHCV Coinfection1
Not AvailableActive Not RecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit; tabletOral
Kit
TabletOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6703403Yes1996-12-262016-12-26Us
US6037157Yes1996-12-262016-12-26Us
US7364752Yes2001-05-102021-05-10Us
US7148359Yes2000-01-192020-01-19Us
US8268349Yes2005-02-252025-02-25Us
US8399015Yes2005-02-252025-02-25Us
US9139536No2008-11-092028-11-09Us
US8685984No2012-09-042032-09-04Us
US8466159No2012-09-042032-09-04Us
US8642538No2009-09-102029-09-10Us
US8501238No2008-09-172028-09-17Us
US8680106No2012-09-042032-09-04Us
US8492386No2012-09-042032-09-04Us
US8188104No2009-05-172029-05-17Us
US9006387No2010-06-102030-06-10Us
US9044480No2011-04-102031-04-10Us
US8686026No2011-06-092031-06-09Us
US8420596Yes2011-10-102031-10-10Us
US8691938No2012-04-132032-04-13Us
US9629841No2013-10-182033-10-18Us
US9333204No2015-01-022035-01-02Us
US9744170No2015-01-022035-01-02Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00193 mg/mLALOGPS
logP5.72ALOGPS
logP7.49ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)12.77ChemAxon
pKa (Strongest Basic)2.16ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area178.72 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity250.79 m3·mol-1ChemAxon
Polarizability99.1 Å3ChemAxon
Number of Rings6ChemAxon
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 dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Valine and derivatives / Proline and derivatives / Alpha amino acid amides / Phenylpyrrolidines / Phenylpropanes / Anilides / Pyrrolidinecarboxamides / Aniline and substituted anilines / N-arylamides / N-acylpyrrolidines
show 12 more
Substituents
Alpha-dipeptide / Valine or derivatives / Proline or derivatives / Alpha-amino acid amide / 1-phenylpyrrolidine / 2-phenylpyrrolidine / Alpha-amino acid or derivatives / Phenylpropane / Anilide / N-acylpyrrolidine
show 31 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carbamate ester, dipeptide, pyrrolidines, ring assembly, aromatic amide (CHEBI:85183)

Targets

Kind
Protein
Organism
Hepatitis C virus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Not Available
Gene Name
NS5A
Uniprot ID
Q5L478
Uniprot Name
Nonstructural protein 5A
Molecular Weight
48598.34 Da
References
  1. DeGoey DA, Randolph JT, Liu D, Pratt J, Hutchins C, Donner P, Krueger AC, Matulenko M, Patel S, Motter CE, Nelson L, Keddy R, Tufano M, Caspi DD, Krishnan P, Mistry N, Koev G, Reisch TJ, Mondal R, Pilot-Matias T, Gao Y, Beno DW, Maring CJ, Molla A, Dumas E, Campbell A, Williams L, Collins C, Wagner R, Kati WM: Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014 Mar 13;57(5):2047-57. doi: 10.1021/jm401398x. Epub 2014 Jan 15. [PubMed:24400777]

Enzymes

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
References
  1. Shen J, Serby M, Surber B, Lee AJ, Ma J, Badri P, Menon R, Kavetskaia O, de Morais SM, Sydor J, Fischer V: Metabolism and Disposition of Pan-Genotypic Inhibitor of Hepatitis C Virus NS5A Ombitasvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1148-57. doi: 10.1124/dmd.115.067496. Epub 2016 May 13. [PubMed:27179128]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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. Keating GM: Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection. Drugs. 2016 Aug;76(12):1203-11. doi: 10.1007/s40265-016-0612-1. [PubMed:27401997]
2. UDP-glucuronosyltransferase 1A1
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. Keating GM: Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection. Drugs. 2016 Aug;76(12):1203-11. doi: 10.1007/s40265-016-0612-1. [PubMed:27401997]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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

Drug created on October 30, 2015 09:54 / Updated on November 09, 2017 04:49