Talazoparib
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MedKoo CAT#: 204710

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.


Price and Availability

Size
Price

25mg
USD 110
200mg
USD 550
2g
USD 3850
Size
Price

50mg
USD 190
500mg
USD 1150
5g
USD 7450
Size
Price

100mg
USD 350
1g
USD 2150

Talazoparib free base (purity>97%, optical purity>98%), is in stock. The same day shipping out after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 204710
Name: Talazoparib
CAS#: 1207456-01-6 (free base)
Chemical Formula: C19H14F2N6O
Exact Mass: 380.11972
Molecular Weight: 380.35
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


Technical Data

Appearance:
White solid powder

Purity:
>97% (or refer to the Certificate of Analysis)

Certificate of Analysis:

Safety Data Sheet (MSDS):

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).

Harmonized System Code:
2934.99.90.01


Additional Information

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.


References

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.