Details of the Drug

General Information of Drug (ID: DMLYGH4)

• Drug Name: MK-4827
• Synonyms: 1038915-60-4; (S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide; UNII-HMC2H89N35; HMC2H89N35; CHEMBL1094636; 2-{4-[(3s)-piperidin-3-yl]phenyl}-2h-indazole-7-carboxamide; MK4827; MK 4827; Niraparib [USAN:INN]; 2-{4-[(3S)-piperidin-3-yl]phenyl}indazole-7-carboxamide; 2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxamide; MK 4827 (Base); Niraparib (USAN); Zejula (TN); MK-4827(Niraparib); SCHEMBL1421875; GTPL8275; CTK8B9123; EX-A290; DTXSID50146129; MolPort-023-219-142; ZINC43206370; BDBM50316226

Indication

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 3	[1]
Breast cancer	2C60-2C65	Phase 2	[2]
Ewing sarcoma	2B52	Phase 1	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 320.4
  Logarithm of the Partition Coefficient (xlogp); 2.2
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Clearance: The total clearance of drug is 16.2 L/h []
  Half-life: The concentration or amount of drug in body reduced by one-half in 36 hours [3]
  Metabolism: The drug is metabolized via the carboxylesterases (CEs) to form a major inactive metabolite []
  Vd: The volume of distribution (Vd) of drug is 1220 L []
• Chemical Identifiers:
  Formula: C19H20N4O
  IUPAC Name: 2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxamide
  Canonical SMILES: C1C[C@H](CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N
  InChI: 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
• Cross-matching ID:
  PubChem CID: 24958200
  CAS Number: 1038915-60-4
  DrugBank ID: DB11793
  TTD ID: D00BMF
  INTEDE ID: DR1164
  ACDINA ID: D00471
• 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
Poly [ADP-ribose] polymerase (PARP)	TTEBCY8	NOUNIPROTAC	Modulator	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Substrate	[5]
Carboxylesterase 1 (CES1) Main DME	DEB30C5	EST1_HUMAN	Substrate	[6]
Beta-glucuronidase (GUSB)	DEP54UE	BGLR_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Gene/Protein Processing	[7]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from MK-4827 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[8]
Ag-221	DMS0ZBI	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Ag-221.	BCR-ABL1-negative chronic myeloid leukaemia [2A41]	[8]
Erdafitinib	DMI782S	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[9]
PF-04449913	DMSB068	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[10]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of MK-4827 and Tazemetostat.	Follicular lymphoma [2A80]	[10]
Arry-162	DM1P6FR	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[8]
Ubrogepant	DM749I3	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[11]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[12]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of MK-4827 and Siponimod.	Multiple sclerosis [8A40]	[8]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of MK-4827 and Ocrelizumab.	Multiple sclerosis [8A40]	[13]
Darolutamide	DMV7YFT	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Darolutamide.	Prostate cancer [2C82]	[14]
Tedizolid	DMG2SKR	Moderate	Decreased clearance of MK-4827 due to the transporter inhibition by Tedizolid.	Skin and skin-structure infection [1F28-1G0Z]	[10]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of MK-4827 and Betrixaban.	Venous thromboembolism [BD72]	[10]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Erythrosine sodium anhydrous	E00324	27872	Colorant
FD&C blue no. 1	E00263	19700	Colorant
FD&C yellow no. 5 free acid	E00246	16014	Colorant
Hydrazine yellow	E00409	164825	Colorant
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Ammonia	E00007	222	Alkalizing agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Ethanol	E00023	702	Antimicrobial preservative; Penetration agent; Solvent
Ferric oxide black	E00522	16211978	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
Potassium hydroxide	E00233	14797	Alkalizing agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent
Shellac	E00695	Not Available	Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Niraparib 100 mg capsule	100 mg	Oral Capsule	Oral
Niraparib Tosylate 100mg capsule	100mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [5] 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.
• [6] Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
• [7] Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.
• [8] Cerner Multum, Inc. "Australian Product Information.".
• [9] Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [12] Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
• [13] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [14] Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.