Simeprevir

Identification

Summary

Simeprevir is a direct-acting antiviral agent that inhibits HCV NS3/4A protease to treat chronic hepatitis C virus (HCV) infection in adults with HCV genotype 1 or 4.

Generic Name

Simeprevir

DrugBank Accession Number

DB06290

Background

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.

Type

Small Molecule

Groups

Approved

Structure

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MOLSDFPDBSMILESInChI

Similar Structures

Structure for Simeprevir (DB06290)

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Weight

Average: 749.939
Monoisotopic: 749.291690263

Chemical Formula

C₃₈H₄₇N₅O₇S₂

Synonyms

• Simeprevir

External IDs

• TMC 435
• TMC 435350
• TMC-435
• TMC-435350
• TMC435

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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.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to treat	Chronic hepatitis c genotype 1	Regimen in combination with: Sofosbuvir (DB08934)	••••••••••••
Used in combination to treat	Chronic hepatitis c genotype 1	Regimen in combination with: Peginterferon alfa-2b (DB00022), Ribavirin (DB00811)	••••••••••••
Used in combination to treat	Chronic hepatitis c genotype 1	Regimen in combination with: Peginterferon alfa-2a (DB00008), Ribavirin (DB00811)	••••••••••••
Used in combination to treat	Chronic hepatitis c genotype 4	Regimen in combination with: Ribavirin (DB00811), Peginterferon alfa-2b (DB00022)	••••••••••••
Used in combination to treat	Chronic hepatitis c genotype 4	Regimen in combination with: Peginterferon alfa-2a (DB00008), Ribavirin (DB00811)	••••••••••••

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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 NS5B 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.

Target	Actions	Organism
ANS3 protease	inhibitor	Hepatitis C Virus
ANS3/4A protein	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.

Adverse Effects

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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.

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	The metabolism of 1,2-Benzodiazepine can be decreased when combined with Simeprevir.
Abametapir	The serum concentration of Simeprevir can be increased when it is combined with Abametapir.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Simeprevir.
Abiraterone	The metabolism of Simeprevir can be decreased when combined with Abiraterone.
Abrocitinib	The serum concentration of Simeprevir can be increased when it is combined with Abrocitinib.

Food Interactions

• Take with food.

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Simeprevir sodium	16U7H60184	1241946-89-3	LLXQGDWGCCKOQP-MVZLLIIPSA-M

International/Other Brands

Olysio

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Galexos	Capsule	150 mg	Oral	Janssen Pharmaceuticals	2013-11-25	2018-03-31
Olysio	Capsule	150 mg	Oral	Janssen Cilag International Nv	2016-09-08	2018-05-23
Olysio	Capsule	150 mg	Oral	Janssen Cilag International Nv	2016-09-08	2018-05-23
Olysio	Capsule	150 mg/1	Oral	Janssen, Lp	2013-11-22	2018-05-25

Categories

ATC Codes

G01AE10 — Combinations of sulfonamides

• G01AE — Sulfonamides
• G01A — ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
• G01 — GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
• G — GENITO URINARY SYSTEM AND SEX HORMONES

J05AP05 — Simeprevir

• J05AP — Antivirals for treatment of HCV infections
• J05A — DIRECT ACTING ANTIVIRALS
• J05 — ANTIVIRALS FOR SYSTEMIC USE
• J — ANTIINFECTIVES FOR SYSTEMIC USE

Drug Categories

• Anti-Infective Agents
• Antiinfectives for Systemic Use
• Antiviral Agents
• Antivirals for Systemic Use
• Antivirals for treatment of HCV infections
• BCRP/ABCG2 Inhibitors
• BCRP/ABCG2 Substrates
• BSEP/ABCB11 Inhibitors
• Cytochrome P-450 CYP1A2 Inhibitors
• Cytochrome P-450 CYP1A2 Inhibitors (moderate)
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (moderate)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Direct Acting Antivirals
• Drugs causing inadvertant photosensitivity
• Enzyme Inhibitors
• Genito Urinary System and Sex Hormones
• Gynecological Antiinfectives and Antiseptics
• HCV NS3/4A Protease Inhibitors
• HCV Protease Inhibitors
• Heterocyclic Compounds, Fused-Ring
• NS3/4A Protease Inhibitors
• OATP1B1/SLCO1B1 Inhibitors
• OATP1B1/SLCO1B1 Substrates
• OATP1B3 inhibitors
• OATP1B3 substrates
• OATP2B1/SLCO2B1 substrates
• Organic Anion Transporting Polypeptide 1B1 Inhibitors
• Organic Anion Transporting Polypeptide 1B3 Inhibitors
• P-glycoprotein inhibitors
• P-glycoprotein substrates
• Photosensitizing Agents
• Protease Inhibitors
• Sulfonamides
• Sulfones
• Sulfur Compounds

Chemical TaxonomyProvided by Classyfire

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 / Heteroaromatic compounds / Secondary carboxylic acid amides / Lactams / Azacyclic compounds / Carbonyl compounds / Hydrocarbon derivatives / Organic oxides / Organonitrogen compounds / Organopnictogen compounds

show 9 more

Substituents

2,4-disubstituted 1,3-thiazole / Alkyl aryl ether / Alpha-amino acid amide / Alpha-amino acid or derivatives / Aminosulfonyl compound / Anisole / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Cyclopropanecarboxylic acid or derivatives / Ether / Heteroaromatic compound / Hydrocarbon derivative / Lactam / Macrolactam / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organic sulfonic acid or derivatives / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Organosulfonic acid or derivatives / Organosulfur compound / Pyridine / Quinoline / Secondary carboxylic acid amide / Sulfonyl / Tertiary carboxylic acid amide / Thiazole

show 25 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Affected organisms

• Hepatitis C Virus

Chemical Identifiers

UNII

9WS5RD66HZ

CAS number

923604-59-5

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,6R,7Z,15R,17R)-N-(cyclopropanesulfonyl)-17-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.0^{4,6}]octadec-7-ene-4-carboxamide

SMILES

[H][C@]12C[C@]1(NC(=O)[C@]1([H])C[C@H](C[C@@]1([H])C(=O)N(C)CCCC\C=C/2)OC1=CC(=NC2=C1C=CC(OC)=C2C)C1=NC(=CS1)C(C)C)C(=O)NS(=O)(=O)C1CC1

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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
7. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
8. FDA Approved Drug Products: OLYSIO (simeprevir) capsules for oral use (November 2017) [Link]

External Links

KEGG Drug

D10081

PubChem Compound

24873435

PubChem Substance

175427067

ChemSpider

23331536

BindingDB

50336504

RxNav

1482790

ChEBI

134743

ChEMBL

CHEMBL501849

ZINC

ZINC000085540268

PDBe Ligand

30B

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Simeprevir

PDB Entries

3kee / 8hnh

FDA label

Download (1.31 MB)

MSDS

Download (57.5 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection	2
4	Completed	Treatment	Cirrhosis of the Liver	1
4	Completed	Treatment	Hepatitis C Virus (HCV) Infection	3
4	Withdrawn	Treatment	Chronic Hepatitis C Virus (HCV) Infection / HIV CDC Category A1	1
4	Withdrawn	Treatment	PT-NANBH	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Capsule	Oral	150 mg
Capsule	Oral	150 mg/1
Capsule	Oral

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US8349869	No	2013-01-08	2026-07-28
US8148399	No	2012-04-03	2029-09-05
US8754106	No	2014-06-17	2026-07-28
US8741926	No	2014-06-03	2026-07-28
US9040562	No	2015-05-26	2026-07-28
US7671032	No	2010-03-02	2025-05-19
US9623022	No	2017-04-18	2026-07-28
US9353103	No	2016-05-31	2026-07-28
US9856265	No	2018-01-02	2026-07-28

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	225	MSDS
water solubility	Insoluble	FDA Label

Predicted Properties

Property	Value	Source
Water Solubility	0.00303 mg/mL	ALOGPS
logP	4.69	ALOGPS
logP	4.56	Chemaxon
logS	-5.4	ALOGPS
pKa (Strongest Acidic)	3.77	Chemaxon
pKa (Strongest Basic)	1.61	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	9	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	156.89 Å2	Chemaxon
Rotatable Bond Count	7	Chemaxon
Refractivity	206.95 m3·mol-1	Chemaxon
Polarizability	80.38 Å3	Chemaxon
Number of Rings	7	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0udi-0000004900-d8f44a9cae79781a833b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0002-0100300900-acb37a023744ee8fcecc
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0udi-0000009100-dfb866d30efcd107acb1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0002-1100017900-5f486902cd4be102b521
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0f79-3581114900-fd1a3344f2ac3831593c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-002s-4301496600-5c211c129bbcb300ece9

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	249.47362	predicted	DeepCCS 1.0 (2019)
[M+H]+	251.19734	predicted	DeepCCS 1.0 (2019)
[M+Na]+	257.5263	predicted	DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.

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Details1. NS3 protease

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. [Article]
2. FDA Approved Drug Products: OLYSIO (simeprevir) capsules for oral use (November 2017) [Link]

Details2. NS3/4A protein

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

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. [Article]
2. FDA Approved Drug Products: OLYSIO (simeprevir) capsules for oral use (November 2017) [Link]

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Drug created at March 19, 2008 16:22 / Updated at February 20, 2024 23:54