OLAPARIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H23FN4O3
Molecular Weight	434.4637
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc2c(c1)c(Cc3ccc(c(c3)C(=O)N4CCN(CC4)C(=O)C5CC5)F)nnc2O

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

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 5 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 7687	1.94 nM [IC50]
Poly [ADP-ribose] polymerase 2 12 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 7687
Poly [ADP-ribose] polymerase 3 1 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 7687

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ovarian cancer 144 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf	Primary		Approved 7968	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 1.4189472E12

C_max

Value	Dose	Analyte	Population
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
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
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
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
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:

AUC

Value	Dose	Analyte	Population
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
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
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
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
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:
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:
43.9499999999999 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:
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:

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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 Page: p. 8	unhealthy n = 52 Health Status: unhealthy Condition: advanced solid tumors Population Size: 52 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf Page: p. 8	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf Page: p. 8
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 n = 195 Health Status: unhealthy Condition: gBRCAm ovarian cancer Population Size: 195 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 n = 195 Health Status: unhealthy Condition: gBRCAm ovarian cancer Population Size: 195 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 Page: p. 99	unhealthy n = 195 Health Status: unhealthy Condition: gBRCAm ovarian cancer Population Size: 195 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208558Orig1s000MultidisciplineR.pdf Page: p. 99	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 Page: p. 99
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 n = 223 Health Status: unhealthy Condition: gBRCA-mutated advanced ovarian cancer Population Size: 223 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 Condition: gBRCA-mutated advanced ovarian cancer 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 n = 223 Health Status: unhealthy Condition: gBRCA-mutated advanced ovarian cancer Population Size: 223 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
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 n = 2618 Health Status: unhealthy Condition: gBRCA-mutated advanced ovarian cancer Population Size: 2618 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

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 657	inducer 343 inhibitor 1318	inhibitor 1421	inhibitor 1359

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT 2 OCT1 473 OCT2 582 OAT3 570 MATE1 290 MATE2 258 OATP1B1 698 MRP2 341 CYP1A2 1268 CYP2A6 594 CYP2B6 679 CYP2C8 761 CYP2C19 1215 CYP2E1 761 CYP3A 175 BCRP 574 P-gp 1087	CYP3A 154 CYP2A6 452 CYP1A1 302 P-gp 1222 BCRP 461	CYP2B6 486 CYP1A2 618 CYP2C19 260 CYP3A 102

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1406	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2A6 625	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2B6 845	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2C19 1277	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2C8 810	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2C9 1362	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2D6 1455	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP2E1 841	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no [Inhibition >100 uM]
CYP1A2 1406	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
CYP2C19 1277	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
CYP2C9 1362	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
CYP3A 244	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	no
P-gp 1253	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	no
OAT3 572	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 18.4 uM]
OCT2 583	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 19.9 uM]
OATP1B1 713	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 20.3 uM]
OCT1 488	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 37.9 uM]
MATE2 258	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 47.1 uM]
MATE1 291	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes [IC50 5.5 uM]
CYP3A 244	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	yes [Inhibition 100 uM]
BCRP 639	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
CYP2B6 845	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=33 Page: -	yes
CYP3A4 1461	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=79 Page: -	yes
MRP2 421	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=35 Page: -	yes
OAT 2	inhibitor 2612 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 461	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	no
CYP1A1 302	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=29 Page: -	yes
CYP2A6 452	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=29 Page: -	yes
P-gp 1222	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206162Orig1s000ClinPharmR.pdf#page=34 Page: -	yes
CYP3A 154	substrate 2751 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 1391	inhibitor 1373 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
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
eMolecules	31526131	https://www.emolecules.com/cgi-bin/more?vid=31526131

PubMed

Title	Date	PubMed
High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs.	2008 Nov 4	18971340
PARP inhibitors and the treatment of breast cancer: beyond BRCA1/2?	2009	20017885
Genomic profiling of breast tumours in relation to BRCA abnormalities and phenotypes.	2009	19589159
BRCA1/2 genetic background-based therapeutic tailoring of human ovarian cancer: hope or reality?	2009 Oct 13	19825178
Recent advances in managing triple-negative breast cancers.	2009 Sep 28	20948704
Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms.	2010	20459590
Targeted therapies in epithelial ovarian cancer.	2010	20111741
A current review of targeted therapeutics for ovarian cancer.	2010	20069122
Are current development programs realising the full potential of new agents?	2010 Dec 20	21172086
A high-throughput pharmaceutical screen identifies compounds with specific toxicity against BRCA2-deficient tumors.	2010 Jan 1	20008842
[Treatment with oral agents for breast cancer].	2010 Jul	20647699
Poly(adp-ribose) polymerase inhibitors: a novel drug class with a promising future.	2010 Mar-Apr	20404603
Multiple roles of BRIT1/MCPH1 in DNA damage response, DNA repair, and cancer suppression.	2010 May	20376879
Molecule of the month. Olaparib.	2010 Nov	21152454
Treatment options for patients with triple-negative breast cancer.	2010 Oct 27	20979652
Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype.	2010 Oct 5	20920367
Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil.	2011	22194930
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.	2012 Nov 1	23118055
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework.	2014 Jun	24833294
5-Fluorouracil-induced RNA stress engages a TRAIL-DISC-dependent apoptosis axis facilitated by p53.	2015 Dec 22	26544897

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

Name

Type

Language

OLAPARIB

Official Name

English

AZD2281

Code

English

KEYLYNK-010 COMPONENT OLAPARIB

Code

English

OLAPARIB [USAN]

Common Name

English

OLAPARIB [ORANGE BOOK]

Common Name

English

OLAPARIB [WHO-DD]

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 COMPONENT OF KEYLYNK-010

Code

English

OLAPARIB [MART.]

Common Name

English

AZ-2281

Code

English

Classification Tree Code System Code

NDF-RT

N0000191623