Talazoparib tosylate
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MedKoo CAT#: 206970

CAS#: 1373431-65-2 (tosylate)

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.

Chemical Structure

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Talazoparib tosylate
CAS# 1373431-65-2 (tosylate)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206970
Name: Talazoparib tosylate
CAS#: 1373431-65-2 (tosylate)
Chemical Formula: C26H22F2N6O4S
Exact Mass: 0.00
Molecular Weight: 552.557
Elemental Analysis: C, 56.52; H, 4.01; F, 6.88; N, 15.21; O, 11.58; S, 5.80

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 220 Ready to ship
50mg USD 350 Ready to ship
100mg USD 600 Ready to ship
200mg USD 1050 Ready to ship
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Related CAS #: 1373431-65-2 (tosylate)   1207456-01-6 (free base)   1207454-56-5 (racemic),  

Synonym: Talazoparib tosylate; BMN673; BMN673; 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 tosylate

InChi Key: QUQKKHBYEFLEHK-QNBGGDODSA-N

InChi Code: InChI=1S/C19H14F2N6O.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h2-8,15-16,24H,1H3,(H,26,28);2-5H,1H3,(H,8,9,10)/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.OS(=O)(C6=CC=C(C)C=C6)=O

Appearance: Solid powder

Purity: >98% (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

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: . PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks.

Biological target: Talazoparib tosylate is a PARP1/2 inhibitor with an IC50 of 0.57 nM for PARP1.
In vitro activity: The cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, were investigated in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34- AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. Reference: Cancers (Basel). 2019 Oct 3;11(10):1493. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826540/
In vivo activity: To assess the ability of talazoparib to inhibit PARP in vivo, mice implanted with SCLC PDX SCRX-Lu149 (small cell lung cancer cells) were treated with 0.2 mg/kg talazoparib administered by oral gavage. Talazoparib reduced tumor PAR by 37–68% compared to untreated controls (p < 0.0001), with statistically significant reductions in PAR polymerization at 6 (p = 0.02) and 18 hours (p = 0.007) and trends towards significance at 3 (p = 0.13) and 24 hours (p = 0.08). There were no statistically significant differences between treatment time points (Figure 5A). Reference: Clin Cancer Res. 2018 Oct 15;24(20):5143-5152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742772/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 108.0 195.45

Preparing Stock Solutions

The following data is based on the product molecular weight 552.56 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.

Recalculate based on batch purity %
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. Kohl V, Flach J, Naumann N, Brendel S, Kleiner H, Weiss C, Seifarth W, Nowak D, Hofmann WK, Fabarius A, Popp HD. Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies. Cancers (Basel). 2019 Oct 3;11(10):1493. doi: 10.3390/cancers11101493. PMID: 31623402; PMCID: PMC6826540. 2. Laird JH, Lok BH, Ma J, Bell A, de Stanchina E, Poirier JT, Rudin CM. Talazoparib Is a Potent Radiosensitizer in Small Cell Lung Cancer Cell Lines and Xenografts. Clin Cancer Res. 2018 Oct 15;24(20):5143-5152. doi: 10.1158/1078-0432.CCR-18-0401. Epub 2018 Jun 26. PMID: 29945991; PMCID: PMC6742772.
In vitro protocol: 1. Kohl V, Flach J, Naumann N, Brendel S, Kleiner H, Weiss C, Seifarth W, Nowak D, Hofmann WK, Fabarius A, Popp HD. Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies. Cancers (Basel). 2019 Oct 3;11(10):1493. doi: 10.3390/cancers11101493. PMID: 31623402; PMCID: PMC6826540.
In vivo protocol: 1. Laird JH, Lok BH, Ma J, Bell A, de Stanchina E, Poirier JT, Rudin CM. Talazoparib Is a Potent Radiosensitizer in Small Cell Lung Cancer Cell Lines and Xenografts. Clin Cancer Res. 2018 Oct 15;24(20):5143-5152. doi: 10.1158/1078-0432.CCR-18-0401. Epub 2018 Jun 26. PMID: 29945991; PMCID: PMC6742772.

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1: Wu S, Gao F, Zheng S, Zhang C, Martinez-Ledesma E, Ezhilarasan R, Ding J, Li X, Feng N, Multani A, Sulman EP, Verhaak RG, de Groot JF, Heffernan TP, Yung WKA, Koul D. EGFR amplification induces increased DNA damage response and renders selective sensitivity to Talazoparib (PARP inhibitor) in glioblastoma. Clin Cancer Res. 2019 Dec 18. pii: clincanres.2549.2019. doi: 10.1158/1078-0432.CCR-19-2549. [Epub ahead of print] PubMed PMID: 31852834.

2: Heidler CL, Roth EK, Thiemann M, Blattmann C, Perez RL, Huber PE, Kovac M, Amthor B, Neu-Yilik G, Kulozik AE. Prexasertib (LY2606368) reduces clonogenic survival by inducing apoptosis in primary patient-derived osteosarcoma cells and synergizes with cisplatin and talazoparib. Int J Cancer. 2019 Nov 28. doi: 10.1002/ijc.32814. [Epub ahead of print] PubMed PMID: 31782150.

3: Elmeliegy M, Lang I, Smolyarchuk EA, Chung CH, Plotka A, Shi H, Wang D. Evaluation of the effect of P-glycoprotein inhibition and induction on talazoparib disposition in patients with advanced solid tumors. Br J Clin Pharmacol. 2019 Nov 26. doi: 10.1111/bcp.14178. [Epub ahead of print] PubMed PMID: 31770456.

4: Hurvitz SA, Gonçalves A, Rugo HS, Lee KH, Fehrenbacher L, Mina LA, Diab S, Blum JL, Chakrabarti J, Elmeliegy M, DeAnnuntis L, Gauthier E, Czibere A, Tudor IC, Quek RGW, Litton JK, Ettl J. Talazoparib in Patients with a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses from the Phase III EMBRACA Trial. Oncologist. 2019 Nov 25. pii: theoncologist.2019-0493. doi: 10.1634/theoncologist.2019-0493. [Epub ahead of print] PubMed PMID: 31767793.

5: Schafer ES, Rau RE, Berg SL, Liu X, Minard CG, Bishop AJR, Romero JC, Hicks MJ, Nelson MD Jr, Voss S, Reid JM, Fox E, Weigel BJ, Blaney SM. Phase 1/2 trial of talazoparib in combination with temozolomide in children and adolescents with refractory/recurrent solid tumors including Ewing sarcoma: A Children's Oncology Group Phase 1 Consortium study (ADVL1411). Pediatr Blood Cancer. 2020 Feb;67(2):e28073. doi: 10.1002/pbc.28073. Epub 2019 Nov 14. PubMed PMID: 31724813.

6: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548621/ PubMed PMID: 31643933.

7: Kohl V, Flach J, Naumann N, Brendel S, Kleiner H, Weiss C, Seifarth W, Nowak D, Hofmann WK, Fabarius A, Popp HD. Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies. Cancers (Basel). 2019 Oct 3;11(10). pii: E1493. doi: 10.3390/cancers11101493. PubMed PMID: 31623402; PubMed Central PMCID: PMC6826540.

8: Zhang D, Baldwin P, Leal AS, Carapellucci S, Sridhar S, Liby KT. A nano-liposome formulation of the PARP inhibitor Talazoparib enhances treatment efficacy and modulates immune cell populations in mammary tumors of BRCA-deficient mice. Theranostics. 2019 Aug 14;9(21):6224-6238. doi: 10.7150/thno.36281. eCollection 2019. PubMed PMID: 31534547; PubMed Central PMCID: PMC6735511.

9: Ye L, Chen J, Li SL, Zhu YL, Xie S, Du X. UPLC-MS/MS method for the determination of talazoparib in rat plasma and its pharmacokinetic study. J Pharm Biomed Anal. 2020 Jan 5;177:112850. doi: 10.1016/j.jpba.2019.112850. Epub 2019 Aug 31. PubMed PMID: 31499430.

10: Yu Y, Durairaj C, Shi H, Wang DD. Population Pharmacokinetics of Talazoparib in Patients With Advanced Cancer. J Clin Pharmacol. 2019 Sep 6. doi: 10.1002/jcph.1520. [Epub ahead of print] PubMed PMID: 31489639.

11: Litton JK, Scoggins ME, Hess KR, Adrada BE, Murthy RK, Damodaran S, DeSnyder SM, Brewster AM, Barcenas CH, Valero V, Whitman GJ, Schwartz-Gomez J, Mittendorf EA, Thompson AM, Helgason T, Ibrahim N, Piwnica-Worms H, Moulder SL, Arun BK. Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. J Clin Oncol. 2019 Aug 28:JCO1901304. doi: 10.1200/JCO.19.01304. [Epub ahead of print] PubMed PMID: 31461380.

12: Guney Eskiler G. Talazoparib to treat BRCA-positive breast cancer. Drugs Today (Barc). 2019 Jul;55(7):459-467. doi: 10.1358/dot.2019.55.7.3015642. Review. PubMed PMID: 31347614.

13: Exman P, Barroso-Sousa R, Tolaney SM. Evidence to date: talazoparib in the treatment of breast cancer. Onco Targets Ther. 2019 Jul 2;12:5177-5187. doi: 10.2147/OTT.S184971. eCollection 2019. Review. PubMed PMID: 31303769; PubMed Central PMCID: PMC6612288.

14: Laird J, Lok BH, Carney B, Kossatz S, de Stanchina E, Reiner T, Poirier JT, Rudin CM. Positron-Emission Tomographic Imaging of a Fluorine 18-Radiolabeled Poly(ADP-Ribose) Polymerase 1 Inhibitor Monitors the Therapeutic Efficacy of Talazoparib in SCLC Patient-Derived Xenografts. J Thorac Oncol. 2019 Oct;14(10):1743-1752. doi: 10.1016/j.jtho.2019.05.032. Epub 2019 Jun 11. PubMed PMID: 31195178; PubMed Central PMCID: PMC6764879.

15: Baldwin P, Ohman AW, Medina JE, McCarthy ET, Dinulescu DM, Sridhar S. Nanoformulation of Talazoparib Delays Tumor Progression and Ascites Formation in a Late Stage Cancer Model. Front Oncol. 2019 May 10;9:353. doi: 10.3389/fonc.2019.00353. eCollection 2019. PubMed PMID: 31134152; PubMed Central PMCID: PMC6524318.

16: Eskiler GG, Cecener G, Dikmen G, Egeli U, Tunca B. Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro. Curr Drug Deliv. 2019;16(6):511-529. doi: 10.2174/1567201816666190515105532. PubMed PMID: 31113350.

17: Yu Y, Chung CH, Plotka A, Quinn K, Shi H, Pápai Z, Nguyen L, Wang D. A Phase 1 Mass Balance Study of (14) C-Labeled Talazoparib in Patients With Advanced Solid Tumors. J Clin Pharmacol. 2019 Sep;59(9):1195-1203. doi: 10.1002/jcph.1415. Epub 2019 Apr 9. PubMed PMID: 30964553.

18: McCann KE. Advances in the use of PARP inhibitors for BRCA1/2-associated breast cancer: talazoparib. Future Oncol. 2019 May;15(15):1707-1715. doi: 10.2217/fon-2018-0751. Epub 2019 Mar 26. PubMed PMID: 30912451.

19: Hoffman J, Chakrabarti J, Plotka A, Milillo Naraine A, Kanamori D, Moroose R, Nguyen L, Wang D, Wainberg ZA. Talazoparib has no clinically relevant effect on QTc interval in patients with advanced solid tumors. Anticancer Drugs. 2019 Jun;30(5):523-532. doi: 10.1097/CAD.0000000000000772. PubMed PMID: 30875341; PubMed Central PMCID: PMC6485310.

20: DuRoss AN, Neufeld MJ, Landry MR, Rosch JG, Eaton CT, Sahay G, Thomas CR Jr, Sun C. Micellar Formulation of Talazoparib and Buparlisib for Enhanced DNA Damage in Breast Cancer Chemoradiotherapy. ACS Appl Mater Interfaces. 2019 Apr 3;11(13):12342-12356. doi: 10.1021/acsami.9b02408. Epub 2019 Mar 21. PubMed PMID: 30860347.

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.