Identification

Name
Grazoprevir
Accession Number
DB11575
Type
Small Molecule
Groups
Approved
Description

Grazoprevir 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 [6]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Grazoprevir. Grazoprevir is an inhibitor of NS3/4A, a serine protease enzyme, encoded by HCV genotypes 1 and 4 [Synthesis]. These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS3, NS4A, NS4B, NS5A and NS5B [FDA Label]. The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs [4]. Subtitutions at amino acid positions 155, 156, or 168 are known to confer resistance. The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself. Despite this disadvantage Grazoprevir is still effective against HCV particularly when paired with Elbasvir.

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 Grazoprevir as first line therapy in combination with Elbasvir for genotypes 1a, 1b, and 4 of Hepatitis C [4]. Grazoprevir and Elbasvir are used with or without 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 [5].

Grazoprevir is available as a fixed dose combination product with Elbasvir (tradename Zepatier) used for the treatment of chronic Hepatitis C. Approved in January 2016 by the FDA, Zepatier is indicated for the treatment of HCV genotypes 1 and 4 with or without Ribavirin depending on the the presence of resistance associated amino acid substitutions in the NS5A protein and previous treatment failure with Ribavirin, Peginterferon alfa-2a, Peginterferon alfa-2b, or other NS3/4A inhibitors like Boceprevir, Simeprevir, or Telaprevir [FDA Label]. When combined together, Grazoprevir and Elbasvir as the combination product Zepatier have been shown to achieve a SVR between 94% and 97% for genotype 1 and 97% and 100% for genotype 4 after 12 weeks of treatment [6]. It can be used in patients with compensated cirrhosis, human immunodeficiency virus co-infection, or severe kidney disease.

Structure
Thumb
Synonyms
  • (1aR,5S,8S,10R,22aR)-5-tert-butyl-N-{(1R,2S)-1-[(cyclopropanesulfonyl)carbamoyl]-2-ethenylcyclopropyl}-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide
  • Grazoprevir
  • Grazoprevir anhydrous
External IDs
MK 5172 / MK-5172 / MK-5172 ANHYDROUS / MK5172
Product Ingredients
IngredientUNIICASInChI Key
Grazoprevir monohydrate4O2AB118LA1350462-55-3RXSARIJMSJWJLZ-CIAYNJNFSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ZepatierGrazoprevir (100 mg) + Elbasvir (50 mg)Tablet, film coatedOralMerck Sharp & Dohme Limited2016-07-22Not applicableEu
ZepatierGrazoprevir (100 mg) + Elbasvir (50 mg)TabletOralMerck Ltd.2016-01-25Not applicableCanada
ZepatierGrazoprevir (100 mg/1) + Elbasvir (50 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Limited2016-01-28Not applicableUs
Categories
UNII
8YE81R1X1J
CAS number
1350514-68-9
Weight
Average: 766.903
Monoisotopic: 766.335997918
Chemical Formula
C38H50N6O9S
InChI Key
OBMNJSNZOWALQB-NCQNOWPTSA-N
InChI
InChI=1S/C38H50N6O9S/c1-6-22-19-38(22,35(47)43-54(49,50)25-13-14-25)42-32(45)29-18-24-20-44(29)34(46)31(37(2,3)4)41-36(48)53-30-16-21(30)10-8-7-9-11-27-33(52-24)40-28-17-23(51-5)12-15-26(28)39-27/h6,12,15,17,21-22,24-25,29-31H,1,7-11,13-14,16,18-20H2,2-5H3,(H,41,48)(H,42,45)(H,43,47)/t21-,22-,24-,29+,30-,31-,38-/m1/s1
IUPAC Name
(1R,18R,20R,24S,27S)-24-tert-butyl-N-[(1R,2S)-1-[(cyclopropanesulfonyl)-C-hydroxycarbonimidoyl]-2-ethenylcyclopropyl]-22-hydroxy-7-methoxy-25-oxo-2,21-dioxa-4,11,23,26-tetraazapentacyclo[24.2.1.0³,¹².0⁵,¹⁰.0¹⁸,²⁰]nonacosa-3(12),4,6,8,10,22-hexaene-27-carboximidic acid
SMILES
[H][[email protected]@]12C[[email protected]@]1([H])OC(O)=N[[email protected]]([H])(C(=O)N1C[[email protected]@]([H])(C[[email protected]@]1([H])C(O)=N[[email protected]@]1(C[[email protected]@]1([H])C=C)C(O)=NS(=O)(=O)C1CC1)OC1=C(CCCCC2)N=C2C=CC(OC)=CC2=N1)C(C)(C)C

Pharmacology

Indication

Grazoprevir is indicated in combination with Elbasvir (as the fixed dose combination product Zepatier) with or without Ribavirin for treatment of chronic HCV genotypes 1a, 1b, or 4 infection in adults.

Structured Indications
Pharmacodynamics

Grazoprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotypes 1a, 1b, and 4 [FDA Label].

Mechanism of action

Grazoprevir is a second generation NS3/4a protease inhibitor used to inhibit viral HCV replication. NS3/4a protease is an integral part of viral replication and mediates the cleavage the virally encoded polyprotein to mature proteins (NS3, NS4A, NS4B, NS5A and NS5B) [FDA Label]. Grazoprevir inhibits the NS3/4protease enzymes of HCV genotype 1a, 1B, and 4 with IC50 values of 7pM, 4pM, and 62pM, respectively.

TargetActionsOrganism
ANS3/4A protein
antagonist
Hepatitis C virus
Absorption

Grazoprevir reaches peak plasma concentration 0.5-3 hours after administration [FDA Label]. Grazoprevir has an absolute bioavailability of 27%. When taken with food the peak concentration of Grazoprevir increases 2.8 fold but this increase in exposure has not been deemed clinically relevant.

Volume of distribution

Grazoprevir has an estimated apparent volume of distribution of 1250 liters [FDA Label]. It is thought to distribute primarily to the liver with its uptake facilitated by organic anion transporting polypeptide 1B1/3.

Protein binding

Grazoprevir is more than 98.8% bound to plasma proteins [FDA Label]. It binds both human serum albumin and α1-acid glycoprotein.

Metabolism

Grazoprevir is partially eliminated by oxidative metabolism meditated by CYP3A [FDA Label]. No circulating metabolites of have been detected in human plasma.

Route of elimination

Grazoprevir is mainly eliminated in the feces (90%) with very little eliminated in the urine (<1%) [FDA Label].

Half life

The geometric mean apparent terminal half-life for Grazoprevir is 31 hours in HCV-infected subjects [FDA Label].

Clearance

The clearance of Grazoprevir has not been determined [FDA Label].

Toxicity

The most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache, and nausea [FDA Label].

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

Interactions

Drug Interactions
DrugInteractionDrug group
AmiodaroneThe metabolism of Grazoprevir can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Grazoprevir can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Grazoprevir can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Grazoprevir can be decreased when combined with Atomoxetine.Approved
BoceprevirThe metabolism of Grazoprevir can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Grazoprevir can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Grazoprevir can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of Grazoprevir can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Grazoprevir can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of Grazoprevir can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Grazoprevir can be decreased when combined with Clemastine.Approved
CobicistatThe metabolism of Grazoprevir can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Grazoprevir can be increased when it is combined with Conivaptan.Approved, Investigational
DabrafenibThe serum concentration of Grazoprevir can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Grazoprevir can be decreased when combined with Darunavir.Approved
DeferasiroxThe serum concentration of Grazoprevir can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Grazoprevir can be decreased when combined with Delavirdine.Approved
DoxycyclineThe metabolism of Grazoprevir can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
EltrombopagThe serum concentration of Grazoprevir can be increased when it is combined with Eltrombopag.Approved
EnzalutamideThe serum concentration of Grazoprevir can be decreased when it is combined with Enzalutamide.Approved
FosamprenavirThe metabolism of Grazoprevir can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Grazoprevir can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Grazoprevir can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Grazoprevir can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Grazoprevir can be increased when it is combined with Idelalisib.Approved
IndinavirThe metabolism of Grazoprevir can be decreased when combined with Indinavir.Approved
IsradipineThe metabolism of Grazoprevir can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Grazoprevir can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Grazoprevir can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Grazoprevir can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Grazoprevir can be decreased when combined with Lopinavir.Approved
LuliconazoleThe serum concentration of Grazoprevir can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Grazoprevir can be decreased when it is combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Grazoprevir can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Grazoprevir can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Grazoprevir can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Grazoprevir can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Grazoprevir can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Grazoprevir can be increased when combined with Nevirapine.Approved
OlaparibThe metabolism of Grazoprevir can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Grazoprevir can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Grazoprevir can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Grazoprevir can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Grazoprevir can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Grazoprevir can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Grazoprevir can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Grazoprevir can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe serum concentration of Grazoprevir can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Grazoprevir can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Grazoprevir can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Grazoprevir can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Grazoprevir can be decreased when combined with Ritonavir.Approved, Investigational
SaquinavirThe metabolism of Grazoprevir can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Grazoprevir can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Grazoprevir can be decreased when it is combined with Siltuximab.Approved
St. John's WortThe serum concentration of Grazoprevir can be decreased when it is combined with St. John&#39;s Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Grazoprevir can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Grazoprevir can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Grazoprevir can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Grazoprevir can be decreased when combined with Telithromycin.Approved
TeriflunomideThe serum concentration of Grazoprevir can be increased when it is combined with Teriflunomide.Approved
TiclopidineThe metabolism of Grazoprevir can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Grazoprevir can be decreased when it is combined with Tocilizumab.Approved
VoriconazoleThe metabolism of Grazoprevir can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Grazoprevir can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Relative to fasting conditions, the administration of a single dose of grazoprevir + elbasvir (Zapatier) with a high-fat (900 kcal, 500 kcal from fat) meal to healthy subjects resulted in decreases in elbasvir AUC0-inf and Cmax of approximately 11% and 15%, respectively, and increases in grazoprevir AUC0-inf and Cmax of approximately 1.5-fold and 2.8-fold, respectively.

References

Synthesis Reference

Harper S, McCauley JA, Rudd MT, Ferrara M, DiFilippo M, Crescenzi B, Koch U, Petrocchi A, Holloway MK, Butcher JW, Romano JJ, Bush KJ, Gilbert KF, McIntyre CJ, Nguyen KT, Nizi E, Carroll SS, Ludmerer SW, Burlein C, DiMuzio JM, Graham DJ, McHale CM, Stahlhut MW, Olsen DB, Monteagudo E, Cianetti S, Giuliano C, Pucci V, Trainor N, Fandozzi CM, Rowley M, Coleman PJ, Vacca JP, Summa V, Liverton NJ: Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS Med Chem Lett. 2012 Mar 2;3(4):332-6. doi: 10.1021/ml300017p. eCollection 2012 Apr 12.

General References
  1. Gentile I, Buonomo AR, Borgia F, Zappulo E, Castaldo G, Borgia G: MK-5172 : a second-generation protease inhibitor for the treatment of hepatitis C virus infection. Expert Opin Investig Drugs. 2014 May;23(5):719-28. doi: 10.1517/13543784.2014.902049. Epub 2014 Mar 26. [PubMed:24666106]
  2. Harper S, McCauley JA, Rudd MT, Ferrara M, DiFilippo M, Crescenzi B, Koch U, Petrocchi A, Holloway MK, Butcher JW, Romano JJ, Bush KJ, Gilbert KF, McIntyre CJ, Nguyen KT, Nizi E, Carroll SS, Ludmerer SW, Burlein C, DiMuzio JM, Graham DJ, McHale CM, Stahlhut MW, Olsen DB, Monteagudo E, Cianetti S, Giuliano C, Pucci V, Trainor N, Fandozzi CM, Rowley M, Coleman PJ, Vacca JP, Summa V, Liverton NJ: Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS Med Chem Lett. 2012 Mar 2;3(4):332-6. doi: 10.1021/ml300017p. eCollection 2012 Apr 12. [PubMed:24900473]
  3. Summa V, Ludmerer SW, McCauley JA, Fandozzi C, Burlein C, Claudio G, Coleman PJ, Dimuzio JM, Ferrara M, Di Filippo M, Gates AT, Graham DJ, Harper S, Hazuda DJ, Huang Q, McHale C, Monteagudo E, Pucci V, Rowley M, Rudd MT, Soriano A, Stahlhut MW, Vacca JP, Olsen DB, Liverton NJ, Carroll SS: MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother. 2012 Aug;56(8):4161-7. doi: 10.1128/AAC.00324-12. Epub 2012 May 21. [PubMed:22615282]
  4. 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]
  5. 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]
  6. 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
D10639
PubChem Compound
44603531
PubChem Substance
347827989
ChemSpider
28506694
ChEBI
132975
ChEMBL
CHEMBL2063090
PharmGKB
PA166163437
HET
SUE
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Grazoprevir
PDB Entries
3sud / 3sue / 3suf / 3sug
FDA label
Download (441 KB)
MSDS
Download (175 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentChronic Hepatitis C Infection / Transplant, Kidney1
1CompletedTreatmentChronic Hepatitis C Infection3
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Impaired Renal Function1
1WithdrawnDiagnosticChronic Hepatitis C Virus (HCV) Infection1
1, 2RecruitingTreatmentEnd Stage Renal Disease (ESRD)1
1, 2RecruitingTreatmentHeart Failure, Unspecified1
2CompletedTreatmentChronic Hepatitis C Infection8
2CompletedTreatmentChronic Hepatitis C Infection / Digestive System Diseases / Flaviviridae Infections / Hepatitis / Hepatitis, Viral, Human / Liver Diseases / RNA Virus Infections / Virus Diseases1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentHepatitis C Virus (HCV)1
2CompletedTreatmentHepatitis C, Chronic1
2RecruitingTreatmentAcute Hepatitis C / Human Immunodeficiency Virus (HIV)1
2TerminatedTreatmentHepatitis C, Chronic1
2, 3CompletedTreatmentChronic Hepatitis C Infection1
2, 3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2, 3CompletedTreatmentHepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Infection2
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentHepatitis C Infection1
3Not Yet RecruitingTreatmentChronic HCV Infection1
3Not Yet RecruitingTreatmentChronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV)1
3Not Yet RecruitingTreatmentChronic Hepatitis C Infection / Compensated liver disease1
3Not Yet RecruitingTreatmentChronic hepatitis C genotype 1b / Cirrhoses, Liver / Fibrosis, Liver / Metabolic Syndromes1
3RecruitingTreatmentAcute Hepatitis C / Chronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV)1
3RecruitingTreatmentHepatitis C, Chronic1
3WithdrawnTreatmentChronic Hepatitis C Infection1
3WithdrawnTreatmentChronic Hepatitis C Infection / Transplantation, Liver1
4Active Not RecruitingTreatmentChronic Hepatitis C Infection / End-Stage Renal Disease (ESRD)1
4Enrolling by InvitationTreatmentChronic Hepatitis C Infection / Substance Abuse, Intravenous / Substance Use Disorder (SUD)1
4Not Yet RecruitingPreventionChronic Hepatitis C Infection / Renal Failure Chronic1
4Not Yet RecruitingTreatmentChronic Hepatitis C Infection1
4Not Yet RecruitingTreatmentTo Assess the Efficacy of Grazoprevir 100mg and Elbasvir 50mg by Determining the Proportion of Sustained Virological Response 12 Weeks After the End of Therapy1
4RecruitingPreventionRenal Failure1
4RecruitingTreatmentChronic Hepatitis C Infection1
4RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection2
4SuspendedPreventionCardiac Transplant Disorder / Chronic Hepatitis C Infection1
4WithdrawnTreatmentChronic Hepatitis C Infection1
4WithdrawnTreatmentHCV1
Not AvailableEnrolling by InvitationNot AvailableChronic Hepatitis C Infection1
Not AvailableNot Yet RecruitingTreatmentHCV, HCC1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Infection1
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8871759No2011-05-042031-05-04Us
US7973040No2009-07-242029-07-24Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0097 mg/mLALOGPS
logP3.14ALOGPS
logP5.41ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)5.31ChemAxon
pKa (Strongest Basic)1.81ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area205.69 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity195.25 m3·mol-1ChemAxon
Polarizability81.09 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 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 / Cyclopropanecarboxylic acids and derivatives / Pyrazines / Heteroaromatic compounds
show 14 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 / Pyrrolidine carboxylic acid or derivatives / Pyrrolidine-2-carboxamide
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Hepatitis C virus
Pharmacological action
Yes
Actions
Antagonist
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

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

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
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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
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 April 07, 2016 10:40 / Updated on November 09, 2017 04:53