talazoparib   Click here for help

GtoPdb Ligand ID: 8313

Synonyms: BMN-673 | BMN673 | Talzenna®
Approved drug
talazoparib is an approved drug (FDA (2018), EMA (2019))
Compound class: Synthetic organic
Comment: Talazoparib is a PARP inhibitor [8], inhibiting both PARP1 and PARP2 [1,8]. The compound is bioavailable as the tosylate salt (PubChem CID 56966514).
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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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Click here for structure editor
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 4
Hydrogen bond donors 2
Rotatable bonds 2
Topological polar surface area 91.72
Molecular weight 380.12
XLogP 3.54
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 Fc1ccc(cc1)C1N=c2cc(F)cc3c2c(C1c1ncnn1C)[nH][nH]c3=O
Isomeric SMILES Fc1ccc(cc1)[C@H]1N=c2cc(F)cc3c2c([C@@H]1c1ncnn1C)[nH][nH]c3=O
InChI InChI=1S/C19H14F2N6O/c1-27-18(22-8-23-27)15-16(9-2-4-10(20)5-3-9)24-13-7-11(21)6-12-14(13)17(15)25-26-19(12)28/h2-8,15-16,25H,1H3,(H,26,28)/t15-,16-/m1/s1
InChI Key IUEWAGVJRJORLA-HZPDHXFCSA-N
References
1. Aoyagi-Scharber M, Gardberg AS, Yip BK, Wang B, Shen Y, Fitzpatrick PA. (2014)
Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone.
Acta Crystallogr F Struct Biol Commun, 70 (Pt 9): 1143-9. [PMID:25195882]
2. 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]
3. Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M et al.. (2018)
Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial.
Ann Oncol, 29 (9): 1939-1947. [PMID:30124753]
4. FDA. 
FDA approves talazoparib for gBRCAm HER2-negative locally advanced or metastatic breast cancer.
Accessed on 17/10/2018. Modified on 17/10/2018. www.fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm623540.htm?utm_campaign=Oncology%2010%2F16%2F18%20talazoparib&utm_medium=email&utm_source=Eloqua&elqTrackId=3d45c5bae09748aa82b26d0d48f2c15b&elq=7a7bc2e2420240ce9d50fab984b1c731&elqaid=5513&elqat=1&elqCampaignId=4429
5. Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M et al.. (2018)
Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.
N Engl J Med, 379 (8): 753-763. [PMID:30110579]
6. 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]
7. Roche H, Blum J, Eiermann W, Im YH, Martin M, Mina L, Rugo H, Visco F, Zhang C, Lokker N et al.. (2015)
P1.01A phase 3 study of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with advanced breast cancer (EMBRACA).
Ann Oncol, 26 Suppl 2: ii16. [PMID:25795821]
8. Tangutoori S, Baldwin P, Sridhar S. (2015)
PARP inhibitors: A new era of targeted therapy.
Maturitas, 81 (1): 5-9. [PMID:25708226]