Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1164)
Drug Name
Niraparib
Synonyms
Niraparib; Niraparib (MK-4827); Niraparib (USAN); Niraparib [USAN:INN]; SCHEMBL1421875; ZEJULA; ZINC43206370; Zejula (TN); MK 4827; MK 4827 (Base); MK-4827; MK-4827(Niraparib); MK4827; (S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide; 1038915-60-4; 2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxamide; 2-{4-[(3S)-piperidin-3-yl]phenyl}indazole-7-carboxamide; 2-{4-[(3s)-piperidin-3-yl]phenyl}-2h-indazole-7-carboxamide; CHEMBL1094636; CTK8B9123; DTXSID50146129; EX-A290; GTPL8275; HMC2H89N35; MFCD17779309; UNII-HMC2H89N35
Indication Ovarian cancer [ICD11: 2C73] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 320.4 Topological Polar Surface Area 72.9
Heavy Atom Count 24 Rotatable Bond Count 3
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
24958200
PubChem SID
56256045 ; 57487185 ; 103749792 ; 104150587 ; 135265184 ; 135626858 ; 136340151 ; 136349580 ; 136367711 ; 136946461 ; 137232464 ; 138192109 ; 144116229 ; 152258260 ; 160647096 ; 160829563 ; 162038124 ; 162113109 ; 163094037 ; 163394941 ; 163843781 ; 174007122 ; 186007055 ; 189561499 ; 198976487 ; 202829003 ; 204430248 ; 223617456 ; 227634434 ; 247056359 ; 249752894 ; 252080192 ; 252166487 ; 252227886 ; 252300335 ; 252462459
CAS Number
1038915-60-4
TTD Drug ID
D00BMF
Formula
C19H20N4O
Canonical SMILES
C1CC(CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N
InChI
1S/C19H20N4O/c20-19(24)17-5-1-3-15-12-23(22-18(15)17)16-8-6-13(7-9-16)14-4-2-10-21-11-14/h1,3,5-9,12,14,21H,2,4,10-11H2,(H2,20,24)/t14-/m1/s1
InChIKey
PCHKPVIQAHNQLW-CQSZACIVSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Indinavir sulfate metabolite M1 DM000978
118737587
Hydrolysis - Amide Hydrolysis 1 [4] , [5]
Niraparib metabolite M1 DM000978 N. A. Hydrolysis - Amide Hydrolysis 1 [4] , [5]
Niraparib metabolite M10 DM002214 N. A. Unclear 2 [4] , [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001751 Niraparib Niraparib metabolite M1 Hydrolysis - Amide Hydrolysis CES1 [4], [5]
MR001750 Niraparib metabolite M1 Niraparib metabolite M10 Unclear UGT [4], [6]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Beta-glucuronidase (GUSB) DME0106 Homo sapiens
BGLR_HUMAN
3.2.1.31
[2]
Carboxylesterase 1 (CES1) DME0054 Homo sapiens
EST1_HUMAN
3.1.1.1
[2]
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[3]
References
1 Niraparib was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
3 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
4 Human mass balance study and metabolite profiling of (14)C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer Invest New Drugs. 2017 Dec;35(6):751-765. doi: 10.1007/s10637-017-0451-2.
5 Liquid chromatography-tandem mass spectrometry assay for the quantification of niraparib and its metabolite M1 in human plasma and urine J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jan 1;1040:14-21. doi: 10.1016/j.jchromb.2016.11.020.
6 P-Glycoprotein (ABCB1/MDR1) Controls Brain Penetration and Intestinal Disposition of the PARP1/2 Inhibitor Niraparib. Mol Pharm. 2021 Dec 6;18(12):4371-4384. doi: 10.1021/acs.molpharmaceut.1c00553.

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