Talazoparib free base | BMN673 | CAS#1207456-01-6 | PARP Inhibitor

MedKoo Cat#: 204710 | Name: Talazoparib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Talazoparib

CAS#1207456-01-6 (free base)

Theoretical Analysis

MedKoo Cat#: 204710

Name: Talazoparib

CAS#: 1207456-01-6 (free base)

Chemical Formula: C19H14F2N6O

Exact Mass: 380.1197

Molecular Weight: 380.35

Elemental Analysis: C, 60.00; H, 3.71; F, 9.99; N, 22.10; O, 4.21

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 350.00	Ready to ship
100mg	USD 600.00	Ready to ship
200mg	USD 1,050.00	Ready to ship

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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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T21D03P05

QC Data

View QC data: current batch, Lot#T21D03P05

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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.

1: Drew Y, Zenke FT, Curtin NJ. DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications. Nat Rev Drug Discov. 2024 Nov 12. doi: 10.1038/s41573-024-01060-w. Epub ahead of print. PMID: 39533099. 2: Jahan N, Taraba J, Boddicker NJ, Giridhar KV, Leon-Ferre RA, Tevaarwerk AJ, Cathcart-Rake E, O'Sullivan CC, Peethambaram PP, Hobday TJ, Mina LA, Batalini F, Advani P, Sideras K, Haddad TC, Ruddy KJ, Goetz MP, Couch FJ, Yadav S. Real- World Evidence on Prescribing Patterns and Clinical Outcomes of Metastatic Breast Cancer Patients Treated with PARP Inhibitors: The Mayo Clinic Experience. Clin Breast Cancer. 2024 Oct 17:S1526-8209(24)00284-2. doi: 10.1016/j.clbc.2024.10.006. Epub ahead of print. PMID: 39516069. 3: Karim NA, Miao J, Reckamp KL, Gay CM, Byers LA, Zhao YQ, Redman MW, Carrizosa DR, Wang WL, Petty WJ, Mehta K, Faller BA, Agamah ES, Kasbari SS, Malisetti RK, Kumar A, Schallenkamp J, Alluri KC, Gray JE, Kelly K. Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929. J Thorac Oncol. 2024 Nov 4:S1556-0864(24)02431-6. doi: 10.1016/j.jtho.2024.10.021. Epub ahead of print. PMID: 39505259. 4: Azad AA, Fizazi K, Matsubara N, Saad F, De Giorgi U, Joung JY, Fong PCC, Jones RJ, Zschäbitz S, Oldenburg J, Shore ND, Dunshee C, Carles J, Fay AP, Lin X, DeAnnuntis L, Di Santo N, Zielinski MA, Agarwal N. Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study. Eur J Cancer. 2024 Oct 20;213:115078. doi: 10.1016/j.ejca.2024.115078. Epub ahead of print. PMID: 39486165. 5: Agarwal N, Saad F, Azad AA, Mateo J, Matsubara N, Shore ND, Chakrabarti J, Chen HC, Lanzalone S, Niyazov A, Fizazi K. The TALAPRO-3 study design: a plain language summary. Future Oncol. 2024;20(30):2225-2231. doi: 10.1080/14796694.2024.2363131. Epub 2024 Jul 24. PMID: 39451095; PMCID: PMC11524196. 6: Haque M, Shyanti RK, Mishra MK. Targeted therapy approaches for epithelial- mesenchymal transition in triple negative breast cancer. Front Oncol. 2024 Oct 10;14:1431418. doi: 10.3389/fonc.2024.1431418. PMID: 39450256; PMCID: PMC11499239. 7: Cicchiello F, Riva F, Corti F, Maggioni C. L’evoluzione di una neoplasia mammaria luminale in una forma triplo negativo e il suo impatto sul controllo della malattia con sacituzumab govitecan [The evolution of a luminal breast cancer to a triple-negative and its impact on disease control with sacituzumab govitecan.]. Recenti Prog Med. 2024 Oct;115(10):52e-56e. Italian. doi: 10.1701/4357.43479. PMID: 39446008. 8: Castro E, Ellis J, Craigie S, Haltner A, Nazari J, Niyazov A, Samjoo IA. Comparative efficacy and safety of talazoparib plus enzalutamide and other first-line treatments for metastatic castration-resistant prostate cancer. Oncologist. 2024 Oct 19:oyae237. doi: 10.1093/oncolo/oyae237. Epub ahead of print. PMID: 39427229. 9: Sharma N, Bhati A, Aggarwal S, Shah K, Dewangan HK. PARP Pioneers: Using BRCA1/2 Mutation-targeted Inhibition to Revolutionize Breast Cancer Treatment. Curr Pharm Des. 2024 Oct 17. doi: 10.2174/0113816128322894241004051814. Epub ahead of print. PMID: 39421986. 10: Erratum: Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib. JCO Precis Oncol. 2024 Oct;8:e2400676. doi: 10.1200/PO-24-00676. Epub 2024 Oct 16. Erratum for: JCO Precis Oncol. 2024 Aug;8:e2400303. doi: 10.1200/PO.24.00303. PMID: 39413341. 11: Zhang X, Rameika N, Zhong L, Rendo V, Veanes M, Kundu S, Nuciforo S, Dupuis J, Al Azhar M, Tsiara I, Seeburger P, Al Nassralla S, Ljungström V, Svensson R, Stoimenov I, Artursson P, Heim MH, Globisch D, Sjöblom T. Loss of heterozygosity of CYP2D6 enhances the sensitivity of hepatocellular carcinomas to talazoparib. EBioMedicine. 2024 Oct 4;109:105368. doi: 10.1016/j.ebiom.2024.105368. Epub ahead of print. PMID: 39368455; PMCID: PMC11490764. 12: Malik U, Pal D. Isoxazole compounds: Unveiling the synthetic strategy, in- silico SAR & toxicity studies and future perspective as PARP inhibitor in cancer therapy. Eur J Med Chem. 2024 Dec 5;279:116898. doi: 10.1016/j.ejmech.2024.116898. Epub 2024 Sep 24. PMID: 39353240. 13: Meher N, Bidkar AP, Wadhwa A, Bobba KN, Dhrona S, Dasari C, Mu C, Fong COY, Cámara JA, Ali U, Basak M, Bulkley D, Steri V, Fontaine SD, Zhu J, Oskowitz A, Aggarwal RR, Sriram R, Chou J, Wilson DM, Seo Y, Santi DV, Ashley GW, VanBrocklin HF, Flavell RR. PET Imaging Using 89Zr Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention (EPR) in Prostate Cancer. Mol Cancer Ther. 2024 Sep 27. doi: 10.1158/1535-7163.MCT-24-0024. Epub ahead of print. PMID: 39331510. 14: Lloyd J, Zomorodian N, Devgan G, Batten J. Talazoparib Plus Enzalutamide in Patients With HRR-Deficient mCRPC: Practical Implementation Steps for Oncology Nurses and Advanced Practice Providers. Clin J Oncol Nurs. 2024 Sep 17;28(5):483-491. doi: 10.1188/24.CJON.483-491. PMID: 39324718. 15: Huang Y, Chen S, Yao N, Lin S, Zhang J, Xu C, Wu C, Chen G, Zhou D. Molecular mechanism of PARP inhibitor resistance. Oncoscience. 2024 Sep 23;11:69-91. doi: 10.18632/oncoscience.610. PMID: 39318358; PMCID: PMC11420906. 16: Thapa B, De Sarkar N, Giri S, Sharma K, Kim M, Kilari D. Integrating PARP Inhibitors in mCRPC Therapy: Current Strategies and Emerging Trends. Cancer Manag Res. 2024 Sep 17;16:1267-1283. doi: 10.2147/CMAR.S411023. PMID: 39308935; PMCID: PMC11416116. 17: Diossy M, Tisza V, Li H, Sahgal P, Zhou J, Sztupinszki Z, Young D, Nousome D, Kuo C, Jiang J, Chen Y, Ebner R, Sesterhenn IA, Moncur JT, Chesnut GT, Petrovics G, Klus GT, Valcz G, Nuzzo PV, Ribli D, Börcsök J, Prosz A, Krzystanek M, Ried T, Szuts D, Rizwan K, Kaochar S, Pathania S, D'Andrea AD, Csabai I, Srivastava S, Freedman ML, Dobi A, Spisak S, Szallasi Z. Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression. NPJ Precis Oncol. 2024 Sep 19;8(1):208. doi: 10.1038/s41698-024-00705-8. PMID: 39294262; PMCID: PMC11411125. 18: Tharamelveliyil Rajendran A, Dheeraj Rajesh G, Ashtekar H, Sairam A, Kumar P, Vadakkepushpakath AN. Uncovering naringin's anticancer mechanisms in glioblastoma via molecular docking and network pharmacology approaches. Sci Rep. 2024 Sep 14;14(1):21486. doi: 10.1038/s41598-024-72475-z. PMID: 39277626; PMCID: PMC11401857. 19: Valdez BC, Tsimberidou AM, Yuan B, Baysal MA, Chakraborty A, Andersen CR, Andersson BS. Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations. Int J Mol Sci. 2024 Aug 26;25(17):9241. doi: 10.3390/ijms25179241. PMID: 39273190; PMCID: PMC11394699. 20: Obasi J, Sharma K, De Sarkar N, Antonarakis ES, Kilari D. Platinum Chemotherapy After PARP Inhibition in HRR-Deficient Metastatic Castration- Resistant Prostate Cancer. Clin Genitourin Cancer. 2024 Aug 10;22(6):102187. doi: 10.1016/j.clgc.2024.102187. Epub ahead of print. PMID: 39241311.

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.