Simeprevir
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Also known as TMC 435TMC 435350TMC-435TMC-435350Tmc435TMC435350SimeprevirÊSimeprevirÂSimprevir
Summary
Simeprevir (CHEMBL501849) is an approved small molecule (ATC J05AP05); indicated across 4 conditions including chronic hepatitis c virus infection and hepatitis c virus infection.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: J05AP05
- Indications: 4 conditions
- Clinical trials: 84
- Chemistry: 749.9 Da · C38H47N5O7S2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL501849 |
| Name | Simeprevir |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 24873435 |
| ATC | J05AP05 |
| Molecular formula | C38H47N5O7S2 |
| Molecular weight | 749.9 |
| InChIKey | JTZZSQYMACOLNN-VDWJNHBNSA-N |
SMILES: CC1=C(C=CC2=C1N=C(C=C2O[C@@H]3C[C@@H]4[C@@H](C3)C(=O)N(CCCC/C=C\[C@@H]5C[C@]5(NC4=O)C(=O)NS(=O)(=O)C6CC6)C)C7=NC(=CS7)C(C)C)OC
IUPAC name: (1R,4R,6S,7Z,15R,17R)-N-cyclopropylsulfonyl-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[13.3.0.04,6]octadec-7-ene-4-carboxamide
Also known as: Simeprevir, TMC 435, TMC 435350, TMC-435, TMC-435350, Tmc435, TMC435350, SIMEPREVIR, simeprevir, SimeprevirÊ, SimeprevirÂ, Simprevir
Parent form; salt/anhydrous children: CHEMBL3137358
Patent coverage: 804 distinct patent families (1,797 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,792 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| Hepatitis C virus genome polyprotein | Inhibition | 9.44 |
Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Cathepsin S, Replicase polyprotein 1ab.
Bioactivity
ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| P0DTD1 | 8.61 | IC50 | 2.46 | nM | CHEMBL_ACT_25952203 |
| CTSS | 6.1 | IC50 | 800 | nM | CHEMBL_ACT_5209921 |
| P0DTD1 | 5.26 | IC50 | 5500 | nM | CHEMBL_ACT_25708370 |
| P0DTD1 | 5.26 | IC50 | 5500 | nM | CHEMBL_ACT_25952230 |
| P0DTD1 | 5.02 | IC50 | 9600 | nM | CHEMBL_ACT_25708369 |
Target pathways
No target-pathway data for this drug (no mapped target genes).
Indications & clinical
Indications
4 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| chronic hepatitis C virus infection | 3 | MONDO:0005354 | EFO:0004220 |
| hepatitis C virus infection | 3 | MONDO:0005231 | EFO:0003047 |
| viral infectious disease | 3 | MONDO:0005108 | EFO:0000763 |
| chronic kidney disease | 2 | MONDO:0005300 | EFO:0003884 |
Clinical trials
Total trials: 84.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 33 |
| PHASE2 | 21 |
| PHASE3 | 17 |
| PHASE4 | 6 |
| Not specified | 6 |
| PHASE2/PHASE3 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02168361 | PHASE4 | COMPLETED | The SIM-SOF Trial for Hepatitis C |
| NCT02206932 | PHASE4 | WITHDRAWN | A Study of the Safety and Effectiveness of Simeprevir and Sofosbuvir for Patients With HIV and Hepatitis C |
| NCT02214420 | PHASE4 | COMPLETED | SMV + SOF With/Without RBV for IFN-II Patients With CHC |
| NCT02485080 | PHASE4 | WITHDRAWN | Safety, Tolerability, and Efficacy of 24 Weeks Simeprevir+Sofosbuvir for Chronic Hepatitis C Genotype 1 |
| NCT02624063 | PHASE4 | COMPLETED | Randomized Clinical Trial of Sofosbuvir in Combination With Daclatasvir or Simeprevir for 12 Weeks in Non-cirrhotic Subjects Infected With Chronic Hepatitis C Virus Genotype 1 (TNT) |
| NCT02992457 | PHASE4 | COMPLETED | Safety and Efficacy of Sofosbuvir-Based Regimens in the Treatment of Egyptian Patients With Hepatitis C Infection |
| NCT01281839 | PHASE3 | COMPLETED | An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy |
| NCT01288209 | PHASE3 | COMPLETED | A Phase III Study of TMC435 in Genotype 1, Hepatitis C-infected Participants Who Failed to Respond to Previous IFN-based Therapy |
| NCT01289782 | PHASE3 | COMPLETED | An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Patients |
| NCT01290679 | PHASE3 | COMPLETED | An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Participants |
| NCT01290731 | PHASE3 | COMPLETED | A Study of TMC435 in Genotype 1, Hepatitis C-infected Patients Who Relapsed After Previous Interferon (IFN)-Based Therapy |
| NCT01292239 | PHASE3 | COMPLETED | A Phase III Study of TMC435 in Treatment-naive, Genotype 1, Hepatitis C-infected Patients |
| NCT01323244 | PHASE3 | COMPLETED | A Study of TMC435 in Combination With Peginterferon Alfa-2A and Ribavirin for Hepatitis C Virus Genotype-1 Infected Patients Who Participated in a Control Group of a TMC435 Study |
| NCT01366638 | PHASE3 | COMPLETED | A Study of TMC435 in Participants With Genotype 1 Hepatitis C Virus (HCV) Infection |
| NCT01479868 | PHASE3 | COMPLETED | A Study to Assess the Safety, Tolerability and Efficacy of TMC435 Along With Pegylated Interferon Alpha-2a (Pegasys) and Ribavirin (Copegus) Triple Therapy in Chronic Hepatitis C Genotype-1 Infected Patients Co-infected With Human Immunodeficiency Virus-Type 1 |
| NCT01485991 | PHASE3 | COMPLETED | TMC435HPC3001 - An Efficacy, Safety and Tolerability Study for TMC435 vs Telaprevir in Combination With PegINFα-2a and Ribavirin in Chronic Hepatitis C Patients Who Were Null or Partial Responders to Prior PegINFα-2a and Ribavirin Therapy |
| NCT01567735 | PHASE3 | COMPLETED | A Study to Evaluate the Efficacy, Safety and Tolerability of TMC435 in Combination With PegIFN Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naïve or Treatment-Experienced, Chronic Hepatitis C Virus Genotype-4 Infected Patients |
| NCT01725529 | PHASE3 | COMPLETED | An Efficacy, Pharmacokinetics, Safety and Tolerability Study of TMC435 as Part of a Treatment Regimen for Hepatitis C-Infected Patients |
| NCT01846832 | PHASE3 | COMPLETED | A Study of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin in Participants With Chronic HCV Infection |
| NCT02114151 | PHASE3 | COMPLETED | Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis |
| NCT02114177 | PHASE3 | COMPLETED | Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Chronic Hepatitis C Virus Infection Without Cirrhosis |
| NCT02250807 | PHASE3 | COMPLETED | Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Subjects With Chronic Genotype 4 Hepatitis C Virus Infection |
| NCT02771405 | PHASE3 | COMPLETED | Impact of Interferon Free Regimens in Patients With Chronic HCV and Successfully Treated HCC |
| NCT05616598 | PHASE2/PHASE3 | COMPLETED | Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters |
| NCT00561353 | PHASE2 | COMPLETED | A Study of TMC435350 Administered With or Without Standard of Care Therapy in Participants With Genotype 1 Hepatitis C Virus Infection |
| NCT00812331 | PHASE2 | COMPLETED | A Study to Assess the Anti-viral Activity, Safety, Tolerability and Pharmacokinetics of TMC435350 in Participants Infected With Hepatitis C-Virus (HCV) |
| NCT00882908 | PHASE2 | COMPLETED | A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment |
| NCT00980330 | PHASE2 | COMPLETED | A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard Treatment |
| NCT00996476 | PHASE2 | COMPLETED | A Study to Assess the Effectiveness, Safety, and Pharmacokinetics of TMC435 in Combination With Peginterferon Alfa-2a and Ribavirin in Hepatitis-C Infected Patients |
| NCT01466790 | PHASE2 | COMPLETED | A Study of TMC435 in Combination With PSI-7977 (GS7977) in Chronic Hepatitis C Genotype 1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV Treatment-Naive Patients |
| NCT01628692 | PHASE2 | COMPLETED | Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus |
| NCT01724086 | PHASE2 | COMPLETED | A Study to Evaluate the Safety, Tolerability, and Effectiveness of a 12-Week Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Patients Infected With Chronic Genotype 1 Hepatitis C Virus |
| NCT01852604 | PHASE2 | COMPLETED | Samatasvir (IDX719) in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Participants With Chronic Hepatitis C Infection (MK-1894-005) |
| NCT01938625 | PHASE2 | COMPLETED | A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation |
| NCT02165189 | PHASE2 | COMPLETED | An Efficacy and Safety Study of Simeprevir and Sofosbuvir With and Without Ribavirin in Participants With Recurrent Genotype 1 Hepatitis C Post-Orthotopic Liver Transplant |
| NCT02253550 | PHASE2 | COMPLETED | Simeprevir in Combination With Sofosbuvir in Treatment-Naïve or -Experienced Adults With Chronic Genotype 4 Hepatitis C Virus Infection |
| NCT02262728 | PHASE2 | COMPLETED | An Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease |
| NCT02268864 | PHASE2 | COMPLETED | A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants |
| NCT02278419 | PHASE2 | COMPLETED | An Efficacy and Safety Study of a 8 or 12-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive and Experienced Participants With Chronic Genotype 4 Hepatitis C Virus Infection |
| NCT02349048 | PHASE2 | COMPLETED | Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).