Details of the Drug

General Information of Drug (ID: DM8QB1D)

Drug Name

Olaparib

Synonyms

AZD 2281; AZD2281; AZD-2281; Acylpiperazine analogue, 47; KU-0059436; KU-59436; Olaparib, KU-0059436, AZD2281,KU0059436, AZD2281; 4-[(3-{[4-Cyclopropylcarbonyl)piperazin-4-yl]carbonyl}-4-fluorophenyl)methyl]phtalazin-1(2H)-one; 4-[3-(4-Cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one

Indication

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Approved	[1]
Pancreatic cancer	2C10	Phase 3	[2]
Prostate cancer	2C82.0	Phase 3	[2]

Affected Organisms

Humans and other mammals

ATC Code

L01XK01: Olaparib

L01XK: Poly (ADP-ribose) polymerase (PARP) inhibitors

L01X: OTHER ANTINEOPLASTIC AGENTS

L01: ANTINEOPLASTIC AGENTS

L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

434.5

Logarithm of the Partition Coefficient (xlogp)

1.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 25.8 mcgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 4.7 and 9.1 mg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1-3 h [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
Clearance: The total clearance of drug is 4.6 L/h [3]
Elimination: Approximately 86% of the administered dose is recovered after 7 days from which 44% is found in the urine and 42% is obtained in feces [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 5 - 11 hours [3]
Metabolism: The drug is metabolized via the liver []
Vd: The volume of distribution (Vd) of drug is 40.3 L [3]

Chemical Identifiers

Formula: C24H23FN4O3
IUPAC Name: 4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one
Canonical SMILES: C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
InChI: InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)
InChIKey: FDLYAMZZIXQODN-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 23725625
ChEBI ID: CHEMBL521686
CAS Number: 763113-22-0
UNII: WOH1JD9AR8
DrugBank ID: DB09074
TTD ID: D0J9HW
VARIDT ID: DR00221
INTEDE ID: DR1188
ACDINA ID: D00485

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[9]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Drug Response	[10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[11]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Gene/Protein Processing	[9]
DNA mismatch repair protein Msh3 (MSH3)	OTD3YPVL	MSH3_HUMAN	Drug Response	[12]
Fumarate hydratase, mitochondrial (FH)	OTEQWU6Q	FUMH_HUMAN	Drug Response	[13]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Gene/Protein Processing	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Gene/Protein Processing	[14]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Post-Translational Modifications	[9]
Succinate dehydrogenase iron-sulfur subunit, mitochondrial (SDHB)	OTRE1M1T	SDHB_HUMAN	Drug Response	[13]

Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Olaparib

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Olaparib caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[15]

Coadministration of a Drug Treating the Disease Different from Olaparib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Olaparib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[16]
Arn-509	DMT81LZ	Major	Increased metabolism of Olaparib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[16]
Oliceridine	DM6MDCF	Moderate	Decreased metabolism of Olaparib caused by Oliceridine mediated inhibition of CYP450 enzyme.	Acute pain [MG31]	[16]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Olaparib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[16]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Olaparib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[16]
Tucatinib	DMBESUA	Major	Decreased metabolism of Olaparib caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[16]
Revefenacin	DMMP5SI	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[17]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Olaparib caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[16]
MK-8228	DMOB58Q	Major	Decreased metabolism of Olaparib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[16]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Increased metabolism of Olaparib caused by Oestradiol valerate and dienogest mediated induction of CYP450 enzyme.	Endometriosis [GA10]	[18]
Stiripentol	DMMSDOY	Major	Decreased metabolism of Olaparib caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Olaparib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Olaparib caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[16]
Ripretinib	DM958QB	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[16]
GS-9857	DMYU6P5	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by GS-9857.	Hepatitis virus infection [1E50-1E51]	[19]
Berotralstat	DMWA2DZ	Major	Decreased metabolism of Olaparib caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[16]
Eluxadoline	DMYZ0P1	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Eluxadoline.	Irritable bowel syndrome [DD91]	[16]
Lurbinectedin	DMEFRTZ	Moderate	Decreased metabolism of Olaparib caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[20]
PF-06463922	DMKM7EW	Major	Increased metabolism of Olaparib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[16]
Capmatinib	DMYCXKL	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Capmatinib.	Lung cancer [2C25]	[21]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Olaparib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[15]
Artesunate	DMR27C8	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Artesunate.	Malaria [1F40-1F45]	[16]
Arry-162	DM1P6FR	Moderate	Decreased metabolism of Olaparib caused by Arry-162 mediated inhibition of UGT.	Melanoma [2C30]	[16]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[22]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[23]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Olaparib and Siponimod.	Multiple sclerosis [8A40]	[16]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Olaparib and Ocrelizumab.	Multiple sclerosis [8A40]	[24]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Olaparib caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[16]
Entrectinib	DMMPTLH	Moderate	Decreased metabolism of Olaparib caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[15]
S-297995	DM26IH8	Moderate	Decreased metabolism of Olaparib caused by S-297995 mediated inhibition of CYP450 enzyme.	Opioid use disorder [6C43]	[16]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Olaparib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[25]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Olaparib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[26]
Relugolix	DMK7IWL	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[16]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Olaparib when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[27]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Olaparib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[16]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Olaparib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[18]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Olaparib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[15]
LEE011	DMMX75K	Major	Decreased metabolism of Olaparib caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[16]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Olaparib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[28]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Olaparib due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[16]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Olaparib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[16]


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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Potassium acetate	E00430	517044	Film/membrane-forming agent
Sodium stearyl fumarate	E00545	23665634	lubricant
Ammonia	E00007	222	Alkalizing agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent


⏷ Show the Full List of 13 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Olaparib 100 mg tablet	100 mg	Oral Tablet	Oral
Olaparib 150 mg tablet	150 mg	Oral Tablet	Oral
Olaparib 50 mg capsule	50 mg	Oral Capsule	Oral

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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: 7519).
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Nivolumab and Olaparib. Hosp Pharm. 2015 May;50(5):356-66. doi: 10.1310/hpj5005-356.
4	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
5	Olaparib New Zealand Data Sheet
6	2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
7	Overexpressed ABCB1 Induces Olaparib-Taxane Cross-Resistance in Advanced Prostate Cancer. Transl Oncol. 2019 May 7;12(7):871-878.
8	Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65.
9	PARP inhibition restores extrinsic apoptotic sensitivity in glioblastoma. PLoS One. 2014 Dec 22;9(12):e114583. doi: 10.1371/journal.pone.0114583. eCollection 2014.
10	Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul;121(7):2750-67. doi: 10.1172/JCI45014.
11	The BET inhibitor INCB054329 reduces homologous recombination efficiency and augments PARP inhibitor activity in ovarian cancer. Gynecol Oncol. 2018 Jun;149(3):575-584. doi: 10.1016/j.ygyno.2018.03.049. Epub 2018 Mar 20.
12	MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin, and a poly(ADP-ribose) polymerase inhibitor. J Biol Chem. 2011 Apr 8;286(14):12157-65. doi: 10.1074/jbc.M110.198804. Epub 2011 Feb 1.
13	Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nat Genet. 2018 Aug;50(8):1086-1092. doi: 10.1038/s41588-018-0170-4. Epub 2018 Jul 16.
14	Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J Med Chem. 2017 Feb 23;60(4):1262-1271. doi: 10.1021/acs.jmedchem.6b00990. Epub 2016 Dec 21.
15	Product Information. Lynparza (olaparib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
16	Cerner Multum, Inc. "Australian Product Information.".
17	Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir). Gilead Sciences, Foster City, CA.
20	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
21	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
22	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
23	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
24	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
25	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
26	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
27	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
28	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.