S63845 - MCL1 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemES63845Cat. No.: HY-100741CAS No.: 1799633-27-4分式: CHClFNOS分量: 829.26作靶點(diǎn): Bcl-2 Family作通路: Apoptosis儲存式: 4C, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (stored undernitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 33.33 mg/mL (40

2、.19 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (2.51 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (2.51 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 S63845有效的選擇性髓細(xì)胞病1 (M

3、CL1) 抑制劑，結(jié)合MCL1的Kd 值為0.19 nM。IC50 & Target MCL10.19 nM (Kd)體外研究 The pro-survival protein myeloid cell leukemia 1 (MCL1) is over expressed in many cancers. S63845 is a smallmolecule that specifically binds with high affinity to the BH3-binding groove of MCL1. S63845 potently killsMCL1-dependent cance

4、r cells, including multiple myeloma, leukaemia and lymphoma cells, by activating theBAX/BAK-dependent mitochondrial apoptotic pathway. The activity of S63845 is next evaluated in a panel ofeight AML cell lines: all lines are sensitive to S63845 (IC50=4-233 nM) 1.體內(nèi)研究 S63845 shows potent anti-tumour

5、activity with an acceptable safety margin as a single agent in severalcancers. Intravenously injected (i.v.) S63845 exerts dose-dependent anti-tumour activity in human multiplemyeloma (H929 and AMO1) xenografts in immunocompromised mice, with maximal tumour growth inhibitionof 114% in the AMO1 model

6、 and 103% in the H929 model. At 25 mg/kg, S63845 induces complete regressionin 7 out of 8 of the mice at 100 days after treatment in the AMO1 model 1.PROTOCOLKinase Assay 1 10 mM HEPES pH 7.4, 175 mM NaCl, 25 M EDTA, 1 mM TCEP, 0.01% P20 and 1% DMSO is used as arunning buffer. The ligand surface is

7、generated using double His-tagged proteins. Serial dilutions of thecompound in buffer are injected over the protein surface. All sample measurements are performed at a flowrate of 30 L per min (injection time 120 s, dissociation time 360 s). The sensor surface is regenerated byconsecutive injections

8、 of 0.35 M EDTA pH 8.0 with 0.1 mg/mL trypsin, 0.5 M imidazole and 45% DMSO (60s, 15 L per min) 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cells are treated with increasing doses of S63845 (typically 0.008, 0.025, 0.04, 0.2, 1, 5 M)

9、for 24 h. Cellsare stained with Annexin V-FITC and propidium iodide, analysed on a FACS Calibur and live cells arerecorded. Data are presented as per cent cell death induction relative to cells cultured in medium alone 1.MCE has not independently confirmed the accuracy of these methods. They are for

10、 reference only.Animal Mice: S63845 is formulated extemporaneously in 25 mM HCl, 20% 2-hydroxy propyl -cyclo dextrin 20%Administration 1 and administrated at the 6.25, 12.5, 25 mg/kg for 0, 20, 40, 60, 80 days. Tumour growth inhibition (TGImax)is calculated 1.MCE has not independently confirmed the

11、accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Clin Cancer Res. 2019 Jul 15;25(14):4455-4465. Clin Cancer Res. 2018 Nov 1;24(21):5458-5470. Clin Res Hepatol Gas. 2018. Dec. Biochem Biophys Res Commun. 2018 Sep 10;503(3):1214-1220.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE Lipids Health Dis. 2019 Feb.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kotschy A, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016 Oct 27;538(7626):477-482.McePdfHeightCaution: Prod