rucaparib   Click here for help

GtoPdb Ligand ID: 7736

Synonyms: AG-014699 | AG014699 | AG14447 | PF-01367338 | Rubraca®
Approved drug PDB Ligand
rucaparib is an approved drug (FDA (2016), EMA (2018))
Compound class: Synthetic organic
Comment: Rucaparib is an orally active poly(ADP-ribose)polymerase (PARP) inhibitor with anti-cancer activity [7]. It was developed by Clovis Oncology.
PARP inhibitors are known to enhance efficacy of anti-cancer therapies such as DNA alkylating agents, topoisomerase I poisons, and ionizing radiation.
Note that in the Thomas et al. paper [7], AG014699 refers to the phosphate salt and AG14447 to the parent molecule.
Rucaparib was accepted for FDA priority review for the treatment of advanced ovarian cancer harbouring mutant BRCA (August 2016).
Note: olaparib was the first PARP inhibitor to be approved for clinical use.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 3
Topological polar surface area 56.92
Molecular weight 323.14
XLogP 3.25
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES CNCc1ccc(cc1)c1[nH]c2c3c1CCNC(=O)c3cc(c2)F
Isomeric SMILES CNCc1ccc(cc1)c1[nH]c2c3c1CCNC(=O)c3cc(c2)F
InChI InChI=1S/C19H18FN3O/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24)
InChI Key HMABYWSNWIZPAG-UHFFFAOYSA-N
References
1. Abida W, Campbell D, Patnaik A, Shapiro JD, Sautois B, Vogelzang NJ, Voog EG, Bryce AH, McDermott R, Ricci F et al.. (2020)
Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study.
Clin Cancer Res, 26 (11): 2487-2496. [PMID:32086346]
2. Calabrese CR, Almassy R, Barton S, Batey MA, Calvert AH, Canan-Koch S, Durkacz BW, Hostomsky Z, Kumpf RA, Kyle S et al.. (2004)
Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361.
J Natl Cancer Inst, 96 (1): 56-67. [PMID:14709739]
3. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G et al.. (2017)
Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet, 390 (10106): 1949-1961. [PMID:28916367]
4. Delaney CA, Wang LZ, Kyle S, White AW, Calvert AH, Curtin NJ, Durkacz BW, Hostomsky Z, Newell DR. (2000)
Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines.
Clin Cancer Res, 6 (7): 2860-7. [PMID:10914735]
5. EMA. 
Rubraca.
Accessed on 07/06/2018. Modified on 07/06/2018. European Medicines Agency, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004272/human_med_002215.jsp&mid=WC0b01ac058001d124
6. Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM et al.. (2017)
Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.
Lancet Oncol, 18 (1): 75-87. [PMID:27908594]
7. Thomas HD, Calabrese CR, Batey MA, Canan S, Hostomsky Z, Kyle S, Maegley KA, Newell DR, Skalitzky D, Wang LZ et al.. (2007)
Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial.
Mol Cancer Ther, 6 (3): 945-56. [PMID:17363489]