Details of the Drug

General Information of Drug (ID: DMLUA9D)

Drug Name
Simeprevir
Synonyms TMC436
Indication
Disease Entry ICD 11 Status REF
Chronic HCV-1 infection 1E51.1 Approved [1]
Renal hypoplasia N.A. Approved [2]
Therapeutic Class
Antiinfective Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 749.9
Logarithm of the Partition Coefficient (xlogp) 4.8
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 41 hours [4]
Metabolism
The drug is metabolized via the hepatic []
Chemical Identifiers
Formula
C38H47N5O7S2
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
Canonical 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
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
InChIKey
JTZZSQYMACOLNN-VDWJNHBNSA-N
Cross-matching ID
PubChem CID
24873435
ChEBI ID
CHEBI:134743
CAS Number
923604-59-5
DrugBank ID
DB06290
TTD ID
D00TLP
VARIDT ID
DR00014
INTEDE ID
DR1484
ACDINA ID
D00623
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A) TTHC7JD POLG_HCV1 Modulator [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [6]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Simeprevir
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Boceprevir DMBSHMF Major Decreased metabolism of Simeprevir caused by Boceprevir mediated inhibition of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [9]
GS-5885 DMSL3DX Major Decreased clearance of Simeprevir due to the transporter inhibition by GS-5885. Hepatitis virus infection [1E50-1E51] [10]
GS-9857 DMYU6P5 Moderate Decreased clearance of Simeprevir due to the transporter inhibition by GS-9857. Hepatitis virus infection [1E50-1E51] [11]
Coadministration of a Drug Treating the Disease Different from Simeprevir (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Midostaurin DMI6E0R Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Midostaurin. Acute myeloid leukaemia [2A60] [12]
Arn-509 DMT81LZ Major Increased metabolism of Simeprevir caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [13]
Gilteritinib DMTI0ZO Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [12]
Troleandomycin DMUZNIG Major Decreased metabolism of Simeprevir caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [9]
Ag-221 DMS0ZBI Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [9]
Talazoparib DM1KS78 Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [14]
Tucatinib DMBESUA Major Decreased metabolism of Simeprevir caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [9]
Revefenacin DMMP5SI Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Revefenacin. Chronic obstructive pulmonary disease [CA22] [15]
Lumacaftor DMCLWDJ Major Increased metabolism of Simeprevir caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [16]
Eslicarbazepine DMZREFQ Major Increased metabolism of Simeprevir caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [13]
Ripretinib DM958QB Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [9]
Brentuximab vedotin DMWLC57 Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Brentuximab vedotin. Hodgkin lymphoma [2B30] [17]
Fostemsavir DM50ILT Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [18]
Cobicistat DM6L4H2 Major Decreased metabolism of Simeprevir caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [9]
Etravirine DMGV8QU Major Increased metabolism of Simeprevir caused by Etravirine mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [13]
Bempedoic acid DM1CI9R Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Bempedoic acid. Hyper-lipoproteinaemia [5C80] [15]
Aliskiren DM1BV7W Moderate Decreased metabolism of Simeprevir caused by Aliskiren mediated inhibition of CYP450 enzyme. Hypertension [BA00-BA04] [16]
Levamlodipine DM92S6N Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Levamlodipine. Hypertension [BA00-BA04] [13]
Eluxadoline DMYZ0P1 Major Decreased clearance of Simeprevir due to the transporter inhibition by Eluxadoline. Irritable bowel syndrome [DD91] [12]
GDC-0199 DMH0QKA Major Decreased clearance of Simeprevir due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [9]
IPI-145 DMWA24P Major Decreased metabolism of Simeprevir caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [9]
Arry-162 DM1P6FR Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Arry-162. Melanoma [2C30] [9]
Ubrogepant DM749I3 Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Ubrogepant. Migraine [8A80] [19]
Fedratinib DM4ZBK6 Major Decreased metabolism of Simeprevir caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [9]
S-297995 DM26IH8 Moderate Decreased metabolism of Simeprevir caused by S-297995 mediated inhibition of CYP450 enzyme. Opioid use disorder [6C43] [12]
Lefamulin DME6G97 Moderate Decreased metabolism of Simeprevir caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [20]
Enzalutamide DMGL19D Major Increased metabolism of Simeprevir caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [13]
Relugolix DMK7IWL Major Decreased clearance of Simeprevir due to the transporter inhibition by Relugolix. Prostate cancer [2C82] [21]
Darolutamide DMV7YFT Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [12]
Voxelotor DMCS6M5 Major Decreased metabolism of Simeprevir caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [9]
PRX-321 DM7YWVT Moderate Decreased metabolism of Simeprevir caused by PRX-321 mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [13]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [22]
Betrixaban DM2C4RF Moderate Decreased clearance of Simeprevir due to the transporter inhibition by Betrixaban. Venous thromboembolism [BD72] [23]
⏷ Show the Full List of 33 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Carmellose sodium E00625 Not Available Disintegrant
Ferric oxide black E00522 16211978 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Gelatin E00630 Not Available Other agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Shellac E00695 Not Available Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent
⏷ Show the Full List of 11 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Simeprevir 150 mg capsule 150 mg Oral Capsule Oral
Simeprevir Sodium eq 150mg base capsule eq 150mg base Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7367).
2 Simeprevir FDA Label
3 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
6 Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. Clin Pharmacokinet. 2016 Feb;55(2):197-208.
7 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
8 Hepatitis C virus direct-acting antiviral drug interactions and use in renal and hepatic impairment. Top Antivir Med. 2015 May-Jun;23(2):92-6.
9 Cerner Multum, Inc. "Australian Product Information.".
10 Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
11 Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir). Gilead Sciences, Foster City, CA.
12 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
13 Product Information. Olysio (simeprevir). Janssen Pharmaceuticals, Titusville, NJ.
14 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
15 Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
16 Canadian Pharmacists Association.
17 Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
18 Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
19 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
20 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
21 Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
22 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
23 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.