BMN-673

• CAT Number: I000776
• CAS Number: 1207456-01-6
• Molecular Formula: C₁₉H₁₄F₂N₆O
• Molecular Weight: 380.35
• Purity: ≥95%
• Target: PARP
• Solubility: DMSO 75 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
• Storage: RT
• IC50: 0.58 nM
• 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)
• InChIKey: IUEWAGVJRJORLA-UHFFFAOYSA-N
• SMILES: CN1C(=NC=N1)C2C(N=C3C=C(C=C4C3=C2NNC4=O)F)C5=CC=C(C=C5)F

BMN-673(CAT: I000776), also known as talazoparib, is a small molecule inhibitor of the enzyme poly (ADP-ribose) polymerase (PARP). PARP is a protein involved in the DNA damage response pathway, repairing damaged DNA and preventing the accumulation of mutations. By inhibiting the activity of PARP, BMN-673 can selectively target cancer cells that have defects in DNA repair pathways, such as those with BRCA mutations. This leads to the accumulation of DNA damage and ultimately cell death. BMN-673 has been approved by the FDA for the treatment of advanced ovarian cancer and breast cancer in patients with BRCA mutations, and it is being studied in clinical trials for the treatment of other types of cancer.

Reference

1: Belz JE, Kumar R, Baldwin P, Ojo NC, Leal AS, Royce DB, Zhang D, van de Ven
AL, Liby KT, Sridhar S. Sustained Release Talazoparib Implants for Localized
Treatment of BRCA1-deficient Breast Cancer. Theranostics. 2017 Sep
26;7(17):4340-4349. doi: 10.7150/thno.18563. eCollection 2017. PubMed PMID:
29158830; PubMed Central PMCID: PMC5695017.

2: de Bono J, Ramanathan RK, Mina L, Chugh R, Glaspy J, Rafii S, Kaye S, Sachdev
J, Heymach J, Smith DC, Henshaw JW, Herriott A, Patterson M, Curtin NJ, Byers LA,
Wainberg ZA. Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor
Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected
Sporadic Cancers. Cancer Discov. 2017 Jun;7(6):620-629. doi:
10.1158/2159-8290.CD-16-1250. Epub 2017 Feb 27. PubMed PMID: 28242752.

3: Wang B, Chu D, Feng Y, Shen Y, Aoyagi-Scharber M, Post LE. Discovery and
Characterization of
(8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-te
trahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel,
Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor,
as an Anticancer Agent. J Med Chem. 2016 Jan 14;59(1):335-57. doi:
10.1021/acs.jmedchem.5b01498. Epub 2015 Dec 23. PubMed PMID: 26652717.

4: Herriott A, Tudhope SJ, Junge G, Rodrigues N, Patterson MJ, Woodhouse L, Lunec
J, Hunter JE, Mulligan EA, Cole M, Allinson LM, Wallis JP, Marshall S, Wang E,
Curtin NJ, Willmore E. PARP1 expression, activity and ex vivo sensitivity to the
PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia.
Oncotarget. 2015 Dec 22;6(41):43978-91. doi: 10.18632/oncotarget.6287. PubMed
PMID: 26539646; PubMed Central PMCID: PMC4791280.

5: Smith MA, Reynolds CP, Kang MH, Kolb EA, Gorlick R, Carol H, Lock RB, Keir ST,
Maris JM, Billups CA, Lyalin D, Kurmasheva RT, Houghton PJ. Synergistic activity
of PARP inhibition by talazoparib (BMN 673) with temozolomide in pediatric cancer
models in the pediatric preclinical testing program. Clin Cancer Res. 2015 Feb
15;21(4):819-32. doi: 10.1158/1078-0432.CCR-14-2572. Epub 2014 Dec 10. Erratum
in: Clin Cancer Res. 2017 Feb 15;23 (4):1118-1119. PubMed PMID: 25500058; PubMed
Central PMCID: PMC4587665.