Talazoparib-tosylate-BMN-673ts-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETalazoparib tosylateCat. No.: HY-108413CAS No.: 1373431-65-2Synonyms: BMN 673ts分式: CHFNOS分量: 552.55作靶點(diǎn): PARP作通路: Cell Cycle/DNA Damage; Epigenetics儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗 D

2、MSO : 108 mg/mL (195.46 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.8098 mL 9.0490 mL 18.0979 mL5 mM 0.3620 mL 1.8098 mL 3.6196 mL10 mM 0.1810 mL 0.9049 mL 1.8098 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實(shí)驗 請根據(jù)您的實(shí)驗動物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢埾扰渲瞥蔚膬湟?/p>

3、，再依次添加助溶劑(為保證實(shí)驗結(jié)果的可靠性，體內(nèi)實(shí)驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.52 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.52 mM); Clear solution1/3 Master of Small Molecules

4、 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Talazoparib tosylate (BMN 673ts)種新型，效，有可服活性的 PARP1/2 抑制劑，抑制PARP1的IC50值為 0.57 nM。IC50 & Target IC50: 0.57 nM (PARP1) 1體外研究 Talazoparib is a potent PARP1/2 inhibitor (PARP1 IC50=0.57 nM), it has no effect on PARG activity atconcentrations up to 1 M. Talazopar

5、ib binds to PARP1 with a dissociation constant (KD) of 0.29 nM.Talazoparib inhibits PARP1 and -2 to a similar extent, with Kis of 1.20 and 0.85 nM, respectively. Talazoparibselectively targets tumor cells with BRCA1, BRCA2, or PTEN gene defects with 20- to more than 200-foldgreater potency than exis

6、ting PARP1/2 inhibitors. Talazoparib targets tumor cells with homologousrecombination gene defects. Tumor models that are either BRCA1-deficient (MX-1 and SUM149) or BRCA2-deficient (Capan-1) are profoundly sensitive to Talazoparib. Talazoparib induces nuclear -H2AX foci atconcentrations as low as 1

7、00 pM 1.體內(nèi)研究 Talazoparib is readily orally bioavailable, with more than 40% absolute oral bioavailability in rats when dosedin carboxylmethyl cellulose. Oral administration of Talazoparib elicits remarkable antitumor activity;xenografted tumors that carry defects in DNA repair due to BRCA mutations

8、or PTEN deficiency areprofoundly sensitive to oral Talazoparib treatment at well-tolerated doses in mice. Synergistic or additiveantitumor effects are also found when Talazoparib is combined with temozolomide, SN38, or platinum drugs1.PROTOCOLCell Assay 1 LoVo cells are treated with Talazoparib (10,

9、 40 nM) and temozolomide (TMZ) either alone or in combinationfor 5 days. Surviving fraction is determined using CellTiter-Glo assay. 1MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 In single-agent studies, olaparib (100 mg

10、/kg), Talazoparib (0.33 or 0.1 mg/kg/d), or vehicle (10% DMAc, 6%Solutol, and 84% PBS) is administered by oral gavage (per os), once daily or Talazoparib (0.165 mg/kg)twice daily for 28 consecutive days. Mice are continuously monitored for 10 more days after last day ofdosing 1.MCE has not independe

11、ntly confirmed the accuracy of these methods. They are for reference only. Cancer Discov. 2017 Sep;7(9):984-998. Mol Cell. 2017 May 18;66(4):503-516.e5. Nat Commun. 2019 Jun 11;10(1):2556. Clin Cancer Res. 2017 Feb 15;23(4):1001-1011.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE ACS Appl Mater I

12、nterfaces. 2019 Apr 3;11(13):12342-12356.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Shen Y, et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency.Clin Cancer Res. 2013 Sep 15;19(18):5003-15.McePdfHeightCaution: Pr