Olaparib

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H23FN4O3
Molecular Weight	434.4628
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=C(CC2=NNC(=O)C3=C2C=CC=C3)C=C1C(=O)N4CCN(CC4)C(=O)C5CC5

InChI

InChIKey=FDLYAMZZIXQODN-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C24H23FN4O3
Molecular Weight	434.4628
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf
Curator's Comment: Description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880823/

Olaparib is an oral inhibitor of poly (ADP-ribose) polymerase enzymes, including PARP1, PARP2, and PARP3 which are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has shown activity in ovarian and breast tumors with known BRCA mutations and was the first FDA approved drug in this class. Lynparza (olaparib) is indicated for treatment of gBRCA-mutated advanced ovarian cancer. Its use together with other chemotherapy medicines can lead to increased effects on the blood resulting in reduction in the numbers of white blood cells and platelets, and anaemia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Poly [ADP-ribose] polymerase 1 7 Target ID: P09874 Gene ID: 142.0 Gene Symbol: PARP1 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/27487106	Inhibitor 8504	1.94 nM [IC50]
Poly [ADP-ribose] polymerase 2 16 Target ID: Q9UGN5 Gene ID: 10038.0 Gene Symbol: PARP2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/27487106	Inhibitor 8504
Poly [ADP-ribose] polymerase 3 4 Target ID: Q9Y6F1 Gene ID: 10039.0 Gene Symbol: PARP3 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/27487106	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ovarian cancer 160 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	Primary		Approved 8583	LYNPARZA Approved Use Monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Launch Date 2014

C_max

Value	Dose	Analyte	Population
6.875 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02430311	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	OLAPARIB plasma	Homo sapiens population: unhealthy age: sex: food status:
6.88 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.97 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.27 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.75 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
43.95 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02430311	300 mg 2 times / day single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	OLAPARIB plasma	Homo sapiens population: unhealthy age: sex: food status:
43.91 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02430311	300 mg 2 times / day single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	OLAPARIB plasma	Homo sapiens population: unhealthy age: sex: food status:
31.68 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02430311	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	OLAPARIB plasma	Homo sapiens population: unhealthy age: sex: food status:
36.37 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02430311	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	OLAPARIB plasma	Homo sapiens population: unhealthy age: sex: food status:
36.53 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02430311	300 mg single, oral dose: 300 mg route of administration: oral experiment type: single co-administered:	OLAPARIB plasma	Homo sapiens population: unhealthy age: sex: food status:
31.7 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.9 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
44 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.7 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.52 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.17 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/30887180	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		OLAPARIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
18% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s001lbl.pdf			OLAPARIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 2 times / day steady, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf
300 mg 2 times / day steady, oral Recommended Dose: 300 mg, 2 times / day Route: oral Route: steady Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208558s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208558s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf	Disc. AE: Anemia, Anemia... AEs leading to discontinuation/dose reduction: Anemia (grade 1-2, 24%) Anemia (grade 3-4, 20%) Neutropenia (9%) Nausea (grade 1-2, 73%) Nausea (grade 3-4, 3%) Vomiting (grade 1-2, 34%) Vomiting (grade 3-4, 3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208558s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf
300 mg 2 times / day steady, oral Recommended Dose: 300 mg, 2 times / day Route: oral Route: steady Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208558s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208558s000lbl.pdf	Disc. AE: Fatigue, Fatigue... Other AEs: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: Fatigue (grade 1-2, 62%) Fatigue (grade 3-4, 4%) Other AEs: Diarrhea (grade 1-2, 31%) Diarrhea (grade 3-4, 2%) Abscess oral (grade 1-2, 19%) Aphthous ulcer (grade 1-2, 19%) Gingival abscess (grade 1-2, 19%) Gingival disorder (grade 1-2, 19%) Gingival pain (grade 1-2, 19%) Gingivitis (grade 1-2, 19%) Mouth ulceration (grade 1-2, 19%) Mucosal infection (grade 1-2, 19%) Mucosal inflammation (grade 1-2, 19%) Oral candidiasis (grade 1-2, 19%) Oral discomfort (grade 1-2, 19%) Oral herpes (grade 1-2, 19%) Oral infection (grade 1-2, 19%) Oral mucosal erythema (grade 1-2, 19%) Oral pain (grade 1-2, 19%) Oropharyngeal discomfort (grade 1-2, 19%) Oropharyngeal pain (grade 1-2, 19%) Abscess oral (grade 3-4, 1%) Aphthous ulcer (grade 3-4, 1%) Gingival abscess (grade 3-4, 1%) Gingival disorder (grade 3-4, 1%) Gingival pain (grade 3-4, 1%) Gingivitis (grade 3-4, 1%) Mouth ulceration (grade 3-4, 1%) Mucosal infection (grade 3-4, 1%) Mucosal inflammation (grade 3-4, 1%) Oral candidiasis (grade 3-4, 1%) Oral discomfort (grade 3-4, 1%) Oral herpes (grade 3-4, 1%) Oral infection (grade 3-4, 1%) Oral mucosal erythema (grade 3-4, 1%) Oral pain (grade 3-4, 1%) Oropharyngeal discomfort (grade 3-4, 1%) Oropharyngeal pain (grade 3-4, 1%) Nasopharyngitis (grade 1-4, 36%) Sinusitis (grade 1-4, 36%) Rhinitis (grade 1-4, 36%) Influenza (grade 1-4, 36%) Decreased appetite (grade 1-4, 22%) Arthralgia (grade 1-4, 30%) Myalgia (grade 1-4, 30%) Dysgeusia (grade 1-4, 27%) Headache (grade 1-2, 25%) Headache (grade 3-4, 1%) Rash (<20%) Cough (<20%) Dyspepsia (<20%) Leukopenia (<20%) Hypomagnesemia (<20%) Dizziness (<20%) Thrombocytopenia (<20%) Creatinine increased (<20%) Lymphopenia (<20%) Edema (<20%) Mean corpuscular volume increased (grade 1-4, 89%) Decreased hemoglobin (grade 1-2, 66%) Decreased hemoglobin (grade 3-4, 17%) Leukocyte count decreased (grade 1-2, 64%) Leukocyte count decreased (grade 3-4, 5%) Lymphocyte count low (grade 1-2, 56%) Lymphocyte count low (grade 3-4, 11%) Absolute neutrophil count decreased (grade 1-2, 44%) Absolute neutrophil count decreased (grade 3-4, 7%) Creatinine serum increased (grade 1-4, 44%) Platelets decreased (grade 1-2, 40%) Platelets decreased (grade 3-4, 2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208558s000lbl.pdf
300 mg 2 times / day steady, oral Recommended Dose: 300 mg, 2 times / day Route: oral Route: steady Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf	Disc. AE: Thrombocytopenia, Myelodysplastic syndrome... AEs leading to discontinuation/dose reduction: Thrombocytopenia (9 patients) Myelodysplastic syndrome (2 patients) Acute myeloid leukemia (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf
400 mg 2 times / day steady, oral Recommended\|MTD Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf	Disc. AE: Nausea, Nausea... AEs leading to discontinuation/dose reduction: Nausea (grade 1-2, 61%) Nausea (grade 3-4, 3%) Vomiting (grade 1-2, 39%) Vomiting (grade 3-4, 4%) Fatigue (grade 1-2, 58%) Fatigue (grade 3-4, 8%) Anemia (grade 1-2, 75%) Anemia (grade 3-4, 15%) Thrombocytopenia (grade 1-2, 27%) Thrombocytopenia (grade 3-4, 3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf
400 mg 2 times / day steady, oral Recommended\|MTD Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	Disc. AE: Myelodysplastic syndrome, Acute myeloid leukemia... AEs leading to discontinuation/dose reduction: Myelodysplastic syndrome (grade 5, <1%) Acute myeloid leukemia (grade 5, <1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf
400 mg 2 times / day steady, oral Recommended\|MTD Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	Disc. AE: Pneumonitis... AEs leading to discontinuation/dose reduction: Pneumonitis (grade 5, <1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf
400 mg 2 times / day steady, oral Recommended\|MTD Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	Other AEs: Anemia, Anemia... Other AEs: Anemia (grade 1-2, 16%) Anemia (grade 3-4, 18%) Abdominal discomfort (grade 1-2, 35%) Abdominal discomfort (grade 3-4, 8%) Decreased appetite (grade 1-2, 21%) Decreased appetite (grade 3-4, 1%) Diarrhea (grade 1-2, 30%) Diarrhea (grade 3-4, 1%) Dyspepsia (grade 1-4, 25%) Asthenia (grade 1-2, 58%) Asthenia (grade 3-4, 8%) Nasopharyngitis (grade 1-4, 26%) Arthralgia (grade 1-4, 21%) Musculoskeletal pain (grade 1-4, 21%) Myalgia (grade 1-4, 22%) Neutropenia (grade 1-2, 18%) Neutropenia (grade 3-4, 7%) Lymphopenia (grade 1-2, 39%) Lymphopenia (grade 3-4, 17%) Mean corpuscular volume increased (grade 1-4, 57%) Creatinine increased (grade 1-2, 28%) Creatinine increased (grade 3-4, 2%) Cough (10-20) Constipation (10-20) Dysgeusia (10-20) Peripheral edema (10-20) Back pain (10-20) Dizziness (10-20) Headache (10-20) Urinary tract infection (10-20) Dyspnea (10-20) Rash (10-20) Leukopenia (1-10) Stomatitis (1-10) Peripheral neuropathy (1-10) Pyrexia (1-10) Hypomagnesemia (1-10) Hyperglycemia (1-10) Anxiety (1-10) Depression (1-10) Insomnia (1-10) Dysuria (1-10) Urinary incontinence (1-10) Vulvovaginal disorder (1-10) Dry skin (1-10) Eczema (1-10) Pruritis (1-10) Hypertension (1-10) Venous thrombosis (1-10) Hot flush (1-10) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087	inducer 440 inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT 4 OCT1 620 OCT2 779 OAT3 747 MATE1 415 MATE2 267 OATP1B1 1079 MRP2 499 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A 227 BCRP 910 P-gp 1741	CYP3A 220 CYP2A6 626 CYP1A1 389 P-gp 2052 BCRP 697	CYP2B6 669 CYP1A2 832 CYP2C19 329 CYP3A 142

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
CYP3A 317	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 18.4 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 19.9 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 20.3 uM]
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 37.9 uM]
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 47.1 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 5.5 uM]
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	yes [Inhibition 100 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	yes
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=79 Page: -	yes
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes
OAT 4	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP1A1 389	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=29 Page: -	yes
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=29 Page: -	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=4 Page: -	yes	yes (co-administration study) Comment: Itraconazole (strong CYP3A inhibitor) increased the AUC of olaparib by 2.7-fold and PBPK modeling predicted that fluconazole (moderate CYP3A inhibitor) would likely increase olaparib AUC by 2-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=4 Page: -

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000PharmR.pdf#page=58 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:83766	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:83766
ChemicalBook	CB02473811	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02473811
ChemicalBook	CB02756176	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02756176
eMolecules	31526131	https://www.emolecules.com/cgi-bin/more?vid=31526131
MolPort	MolPort-009-679-395	https://www.molport.com/shop/molecule-link/MolPort-009-679-395
Selleck Chemicals	AZD2281(Olaparib)	http://www.selleckchem.com/products/AZD2281(Olaparib).html
ZINC	ZINC000040430143	http://zinc15.docking.org/substances/ZINC000040430143

PubMed

Title	Date	PubMed
5-Fluorouracil-induced RNA stress engages a TRAIL-DISC-dependent apoptosis axis facilitated by p53.	2015-12-22	26544897
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.	2015-10-29	26510020
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework.	2014-06	24833294
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.	2012-11-01	23118055
BAP1 loss defines a new class of renal cell carcinoma.	2012-06-10	22683710
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.	2011-07	21633166
5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2).	2011-04-14	21417348
MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin, and a poly(ADP-ribose) polymerase inhibitor.	2011-04-08	21285347
Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil.	2011	22194930
Are current development programs realising the full potential of new agents?	2010-12-20	21172086
BRCA mutations in the management of breast cancer: the state of the art.	2010-12	20956982
The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo.	2010-11-25	20739657
Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699.	2010-11-09	20978505
Molecule of the month. Olaparib.	2010-11	21152454
Targeting poly(ADP-ribose) polymerase activity for cancer therapy.	2010-11	20725763
Treatment options for patients with triple-negative breast cancer.	2010-10-27	20979652
Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination.	2010-10-14	20976249
Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype.	2010-10-05	20920367
New developments in treatment of ovarian carcinoma: focus on trabectedin.	2010-10-01	21188115
Targeted therapies: PARP inhibitor olaparib is safe and effective in patients with BRCA1 and BRCA2 mutations.	2010-10	20922827
Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.	2010-10	20871615
Gateways to clinical trials.	2010-09	21069103
PARP inhibition: targeting the Achilles' heel of DNA repair to treat germline and sporadic ovarian cancers.	2010-09	20485165
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial.	2010-07-24	20609468
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial.	2010-07-24	20609467
[Treatment with oral agents for breast cancer].	2010-07	20647699
Sensitization to radiation and alkylating agents by inhibitors of poly(ADP-ribose) polymerase is enhanced in cells deficient in DNA double-strand break repair.	2010-06	20530711
Society for biomolecular sciences - 16th annual conference & exhibition - advancing the science of drug discovery.	2010-06	20506057
Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval.	2010-05-20	20406929
Does race affect outcomes in triple negative breast cancer?	2010-05-07	20697530
Multiple roles of BRIT1/MCPH1 in DNA damage response, DNA repair, and cancer suppression.	2010-05	20376879
Poly(adp-ribose) polymerase inhibitors: a novel drug class with a promising future.	2010-04-21	20404603
Gateways to clinical trials.	2010-04-13	20383346
Biology-driven cancer drug development: back to the future.	2010-04-12	20385032
Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan.	2010-02-15	20145144
PARP inhibitors in BRCA1/BRCA2 germline mutation carriers with ovarian and breast cancer.	2010-02-11	20948822
ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors.	2010-02	20124459
Prevalence and predictors of loss of wild type BRCA1 in estrogen receptor positive and negative BRCA1-associated breast cancers.	2010	21080930
Triple-negative breast cancer.	2010	21050424
Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone.	2010	21050423
Present and future evolution of advanced breast cancer therapy.	2010	21050422
Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms.	2010	20459590
Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical risk factors and pathologic features.	2010	20149218
Targeted therapy in ovarian cancer.	2010	20130818
Targeted therapies in epithelial ovarian cancer.	2010	20111741
A current review of targeted therapeutics for ovarian cancer.	2010	20069122
The Emerging Role of PARP Inhibitors in the Treatment of Epithelial Ovarian Cancer.	2010	20049345
Recent advances in managing triple-negative breast cancers.	2009-09-28	20948704
Converting cancer mutations into therapeutic opportunities.	2009-09	20049732
Tailored targeted therapy for all: a realistic and worthwhile objective?	2009	20030882

Patents

Sample Use Guides

In Vivo Use Guide

400 mg (eight 50 mg capsules) taken twice daily, for a total daily dose of 800 mg. Continue treatment until disease progression or unacceptable toxicity.

Route of Administration: Oral

In Vitro Use Guide

30-100 nM in SW620 cells

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:03:40 GMT 2025` Edited by `admin` on `Mon Mar 31 18:03:40 GMT 2025`
Record UNII	WOH1JD9AR8
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Olaparib

Official Name

English

AZ-2281

Preferred Name

English

Olaparib [WHO-DD]

Common Name

English

AZD2281

Code

English

KEYLYNK-010 COMPONENT OLAPARIB

Code

English

OLAPARIB [USAN]

Common Name

English

OLAPARIB [ORANGE BOOK]

Common Name

English

NSC-747856

Code

English

OLAPARIB [JAN]

Common Name

English

AZ2281

Code

English

OLAPARIB [VANDF]

Common Name

English

KU-0059436

Code

English

olaparib [INN]

Common Name

English

1(2H)-Phthalazinone, 4-[[3-[[4-(cyclopropylcarbonyl)-1-piperazinyl]carbonyl]-4-fluorophenyl]methyl]-

Systematic Name

English

PIPERAZINE, 1-(CYCLOPROPYLCARBONYL)-4-(5-((3,4-DIHYDRO-4-OXO-1-PHTHALAZINYL)METHYL)-2-FLUOROBENZOYL)-

Systematic Name

English

LYNPARZA

Brand Name

English

4-[(3-{[4-(Cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorophenyl)methyl]phthalazin-1(2H)-one

Systematic Name

English

AZD-2281

Code

English

OLAPARIB [MI]

Common Name

English

KU-59436

Code

English

OLAPARIB [MART.]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000191623