UMI-77 - Bcl-2 Family 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEUMI-77Cat. No.: HY-18628CAS No.: 518303-20-3分式: CHBrNOS分量: 468.34作靶点: Bcl-2 Family作通路: Apoptosis储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 28 mg/mL (59.79 mM)* means soluble, but satur

2、ation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1352 mL 10.6760 mL 21.3520 mL5 mM 0.4270 mL 2.1352 mL 4.2704 mL10 mM 0.2135 mL 1.0676 mL 2.1352 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 UMI-77种选择性的 Mcl-1 抑制剂，对 Mcl-1 具有亲和 (IC50= 0.31 M)。UMI-77 结到 Mcl-1 的

3、BH3结合沟， Ki 值为 490 nM，作于 Bcl-2 家族其他成员的选择性。IC50 & Target Mcl-1 Bfl-1 Bcl-W Bcl-20.49 M (Ki) 5.33 M (Ki) 8.19 M (Ki) 23.83 M (Ki)1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBcl-xL32.99 M (Ki)体外研究 Competitive binding curve of UMI-77 against Mcl-1 is obtained by FP based binding assay using fluoresc

4、entlabeled Bid BH3 peptide with an IC50 of 1.870.22 M. UMI-77 potently inhibits the cell growth of BxPC-3and Panc-1 cell lines with IC50 values of 3.4 M and 4.4 M respectively, and shows 3 to 5 times lesspotency in inhibition of the cell growth of two other tested cell lines MiaPaCa-2 (12.5 M) and A

5、sPC-1 (16.1 M). The cell growth inhibition potency of UMI-77 correlates with the highest expression of Mcl-1 and Bak, andlowest expression of Bcl-xL in the sensitive cell lines, BxPC-3 and Panc-1. Capan-2 cells are showing similarsensitivity to UMI-77 (IC50 of 5.5 M) as BxPC-3 and Panc-1, although h

6、as low Mcl-1 levels 1.体内研究 UMI-77 exhibits moderate metabolic stability with a half-life of 45 minutes.The maximum tolerated dose(MTD) of UMI-77 in SCID mice is determined. Administered 60 mg/kg i.v. for 5 consecutive days per week fortwo weeks does not cause any loss in the animal weight and there

7、is no obvious sign of toxicity during thecourse of the treatment. Increasing the dose to 80 mg/kg show severe animal weight loss (20%), therefore60 mg/kg is used as a therapeutic dose for the in vivo efficacy studies. Daily treatment with UMI-77 for 5consecutive days a week for two weeks results in

8、statistically significant tumor growth inhibition by 65% and56% in comparison with the controls in day 19 (p 1.PROTOCOLCell Assay 1 Human PC cell lines AsPC-1, BxPC-3 and Capan-2 are cultured in RPMI 1640 medium, while Panc-1 andMiaPaCa are cultured in DMEM medium, all supplemented with 10% fetal bo

9、vine serum. The cell growthinhibition after treatment with increasing concentrations of the compounds (e.g., UMI-77; 1,10, and 100 M)is determined by WST-8 assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 For BxPC-3

10、subcutaneous model, 10106 cells are subcutaneously injected into the flanks of 4-5 week oldfemale severe combined immune deficient mice (ICR-SCID). Palpable tumors start to appear in 3-5 weeks.Tumors are measured twice weekly. To prevent any pain or discomfort, mice are euthanized and their tumorsre

11、move once they reach 1800 mg burden. Tumors are then dissected into 50 mg pieces and re-transplantedinto nave ICR-SCID for serial propagation. Animals are treated with either vehicle or UMI-77 given i.v. (60mg/kg) on day three post BxPC-3 transplantation for two weeks (5 days a week). Tumor weight i

12、s recordedthroughout the treatment period. At the end of the treatment period, animals are euthanized and their tumorsharvested for protein isolation and western blot analysis for apoptotic markers.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Abulwerdi F, et al. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014Mar;13(3):565-575.McePdfHeight2/2 Master of Small Molecules 您边的抑制剂师www.MedChem