WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H204710
CAS#: 1207456-01-6 (free base)
Description: Talazoparib, also known as BMN-673 and MDV-3800, is an orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential antineoplastic activity (PARP1 IC50 = 0.57 nmol/L). Talazoparib acts as an inhibitor of poly ADP ribose polymerase(PARP) which aids in single strand DNA repair. Cells that have BRCA1/2 mutations are susceptible to the cytotoxic effects of PARP inhibitors because of an accumulation of DNA damage. Talazoparib is theorized to have a higher potency than olaparib due to the additional mechanism of action called PARP trapping. PARP trapping is the mechanism of action where the PARP molecule is trapped on the DNA, which interferes with the cells ability to replicate. Talazoparib is found to be ~100 fold more efficient in PARP trapping than olaparib. Talazoparib was approved in 2018 by FDA.
Hodoodo Cat#: H204710
Name: Talazoparib
CAS#: 1207456-01-6 (free base)
Chemical Formula: C19H14F2N6O
Exact Mass: 380.12
Molecular Weight: 380.350
Elemental Analysis: C, 60.00; H, 3.71; F, 9.99; N, 22.10; O, 4.21
Related CAS #: 1373431-65-2 (tosylate) 1207456-01-6 (free base) 1207454-56-5 (racemic),
Synonym: BMN673; BMN 673; BMN-673; LT673; LT 673; LT-673; MDV-3800; MDV 3800; MDV3800; Talazoparib; Talzenna.
IUPAC/Chemical Name: (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one
InChi Key: HWGQMRYQVZSGDQ-HZPDHXFCSA-N
InChi Code: 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/h2-8,15-16,24H,1H3,(H,26,28)/t15-,16-/m1/s1
SMILES Code: O=C1NN=C2C3=C1C=C(F)C=C3N[C@H](C4=CC=C(F)C=C4)[C@H]2C5=NC=NN5C
Appearance: White solid powder
Purity: >97% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Talazoparib was approved in October 2018, in the United States and June 2019, in the European Union for germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.
| Biological target: | PARP1 and PARP2 enzyme activity inhibitor with Kis of 1.2 and 0.87 nM, respectively. |
| In vitro activity: | The objective of the present study was to elucidate the effect of BMN 673 (talozoparib) on BRCA1 mutant (HCC1937) and wild-type (MDA-MB-231) triple negative breast cancer (TNBC). The in vitro cytotoxicity results indicated that BMN 673 had considerable inhibitory effects on HCC1937 and MDA-MB-231 cell lines by inducing apoptosis, multicaspase activity, G2/M arrest, and altering the expression levels of apoptosis-related genes (P < 0.01). Additionally, BMN 673 indicated no toxicity on MCF-10A control cells until a certain concentration and incubation time. However, BMN 673, a novel and selective poly ADP ribose polymerase inhibitor, was more potent in TNBC cells bearing BRCA1 mutant than those with wild-type BRCA1. Reference: BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. https://onlinelibrary.wiley.com/doi/abs/10.1002/jbt.22286 |
| In vivo activity: | Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors. Reference: Theranostics. 2017; 7(17): 4340–4349. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695017/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 40.0 | 105.17 | |
| DMF | 25.0 | 65.72 | |
| DMF:PBS (pH 7.2)(1:3) | 0.3 | 0.66 | |
| Ethanol | 0.3 | 0.66 | |
| Water | 0.1 | 0.26 |
The following data is based on the product molecular weight 380.35 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Guney Eskiler G, Cecener G, Egeli U, Tunca B. BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23. PMID: 30672063. 2. 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.CCR14-2572. Epub 2014 Dec 10. Erratum in: Clin Cancer Res. 2017 Feb 15;23 (4):1118-1119. PMID: 25500058; PMCID: PMC4587665 3. 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. PMID: 29158830; PMCID: PMC5695017. |
| In vitro protocol: | 1. Guney Eskiler G, Cecener G, Egeli U, Tunca B. BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23. PMID: 30672063. 2. 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. PMID: 25500058; PMCID: PMC4587665 |
| In vivo protocol: | 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. PMID: 29158830; PMCID: PMC5695017. 2. 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. PMID: 25500058; PMCID: PMC4587665. |
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1. Zhang R, Wang T, Lin J. Synergistic Effect of Bazedoxifene and PARP Inhibitor in the Treatment of Ovarian Cancer Regardless of BRCA Mutation. Anticancer Res. 2021 May;41(5):2277-2286. doi: 10.21873/anticanres.15003. PMID: 33952453.
2. Tang M, Pei G, Su D, Wang C, Feng X, Srivastava M, Chen Z, Zhao Z, Chen J. Genome-wide CRISPR screens reveal cyclin C as synthetic survival target of BRCA2. Nucleic Acids Res. 2021 Jul 21;49(13):7476-7491. doi: 10.1093/nar/gkab540. PMID: 34197614.
