CasNo.1207456-01-6,Talazoparib (BMN 673),(1207456-01-6) Suppliers

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Purity: >97%

Keywords

Talazoparib (BMN 673) LT-673 1207456-01-6

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Biological Activity

Description

Talazoparib (BMN 673, LT-673) is a novel PARP inhibitor with IC50 of 0.57 nM for PARP1 in a cell-free assay. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 3.

Features

Most potent and selective PARPi reported thus far.

Targets

PARP1 [1]
(Cell-free assay)

0.57 nM

In vitro

BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. BMN 673 selectively kills cancer cells with BRCA-1 or BRCA-2 mutations. BMN 673 demonstrates single-agent cytotoxicityin BRCA-1 mutant (MX-1, IC50 = 0.3 nM) and BRCA-2 mutant cells (Capan-1, IC50 = 5 nM). In contrast, in MRC-5 normal human fibroblastand other tumor cell lines with wild-type BRCA-1 and BRCA-2 genes, IC50 of BMN 673 ranges between 90 nM and 1.9 μM. [1] In cultured human cancer cells, BMN 673 also significantly enhances the cytotoxic efficacy of both Temozolomide and SN-38. Off-target molecular screening did not identify significant non-specific activity for this class of PARP inhibitors. [2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
BR5FVB1-Akt	Growth Inhibition Assay	0.1-100 nM	24/48/72 h	inhibits cell proliferation dose dependently	26047697
BR5FVB1-Akt	Apoptosis Assay	0.1-100 nM	72 h	induces apoptosis	26047697
Capan-1	Growth Inhibition Assay			IC50=16.0 ± 5.4 µM	25864590

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	cleaved-PARP / cleaved-caspase3 / γ-H2AX; pKAP1 / pChk2 / pChk1; PD-L1; p-ATM;	29158830 28947502 28167507 30472087
Growth inhibition assay	Cell viability;	29158830
Immunofluorescence	cleaved PARP / 53BP1; RAD51;	28958991 30621214

In vivo

In rat pharmacokinetic studies, BMN 673 displays >50% oralbioavailability and pharmacokinetic properties that enable singledaily dosing. In MX-1 xenograft tumor model studies, daily oral dosingof BMN 673 significantly enhances the antitumor effects ofcytotoxic therapies in a dose-dependent manner. [2]