olaparib   Click here for help

GtoPdb Ligand ID: 7519

Synonyms: AZD-2281 | AZD2281 | Lynparza®
Approved drug PDB Ligand
olaparib is an approved drug (EMA & FDA (2014))
Compound class: Synthetic organic
Comment: Olaparib is an AstraZeneca poly ADP ribose polymerase (PARP) inhibitor [9]. It is discussed in the AZ 2014 review paper [3].
Cancer cells carrying BRCA mutations become more reliant on PARP activity to maintain DNA repair [11], so this enzyme represents a vulnerable target for pharmaceutical intervention in these cancers.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 86.37
Molecular weight 434.18
XLogP 2.44
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=C(N1CCN(CC1)C(=O)c1cc(ccc1F)Cc1n[nH]c(=O)c2c1cccc2)C1CC1
Isomeric SMILES O=C(N1CCN(CC1)C(=O)c1cc(ccc1F)Cc1n[nH]c(=O)c2c1cccc2)C1CC1
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)
InChI Key FDLYAMZZIXQODN-UHFFFAOYSA-N
References
1. Buisson R, Dion-Côté AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, Stasiak A, Xia B, Masson JY. (2010)
Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.
Nat Struct Mol Biol, 17 (10): 1247-54. [PMID:20871615]
2. Clarke N, Wiechno P, Alekseev B, Sala N, Jones R, Kocak I, Chiuri VE, Jassem J, Fléchon A, Redfern C et al.. (2018)
Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial.
Lancet Oncol, 19 (7): 975-986. [PMID:29880291]
3. Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN. (2014)
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework.
Nat Rev Drug Discov, 13 (6): 419-31. [PMID:24833294]
4. Dillon KJ, Smith GC, Martin NM. (2003)
A FlashPlate assay for the identification of PARP-1 inhibitors.
J Biomol Screen, 8 (3): 347-52. [PMID:12857389]
5. Johannes JW, Balazs A, Barratt D, Bista M, Chuba MD, Cosulich S, Critchlow SE, Degorce SL, Di Fruscia P, Edmondson SD et al.. (2021)
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD5305): A PARP1-DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs.
J Med Chem, 64 (19): 14498-14512. [PMID:34570508]
6. Karzai F, VanderWeele D, Madan RA, Owens H, Cordes LM, Hankin A, Couvillon A, Nichols E, Bilusic M, Beshiri ML et al.. (2018)
Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations.
J Immunother Cancer, 6 (1): 141. [PMID:30514390]
7. Ma Y, He L, Huang Q, Zheng S, Zhang Z, Li H, Liu S. (2018)
Response to olaparib in metastatic castration-resistant prostate cancer with germline BRCA2 mutation: a case report.
BMC Med Genet, 19 (1): 185. [PMID:30333000]
8. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N et al.. (2015)
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
N Engl J Med, 373 (18): 1697-708. [PMID:26510020]
9. Menear KA, Adcock C, Boulter R, Cockcroft XL, Copsey L, Cranston A, Dillon KJ, Drzewiecki J, Garman S, Gomez S et al.. (2008)
4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1.
J Med Chem, 51 (20): 6581-91. [PMID:18800822]
10. Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, Ji J, Takeda S, Pommier Y. (2012)
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
Cancer Res, 72 (21): 5588-99. [PMID:23118055]
11. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, Derksen PW, de Bruin M, Zevenhoven J, Lau A et al.. (2008)
High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs.
Proc Natl Acad Sci USA, 105 (44): 17079-84. [PMID:18971340]