UMI-77 is a selective Mcl-1 inhibitor. UMI-77 binds to the BH3-binding groove of Mcl-1 with a Ki of 490 nM and is selective over other members of the Bcl-2 family.

MCL1:490 nM(Ki)

方法：使用UMI-77 （1,10,100μM）处理一组具有不同表达抗凋亡蛋白和促凋亡蛋白的五种 PC 细胞系（MiaPaCa-2，AsPC-1，Panc-1 ，BxPC-3，Capan-2 ）， 并评估了细胞毒性作用。
结果：UMI-77 对 BxPC-3 、Panc-1 、MiaPaCa-2、AsPC-1 、Capan-2 细胞系IC50值分别为（ 3.4 , 4.4 , 12.5, 16.1, 5.5μM）。[1]

方法：使用UMI-77 （60，80mg / kg，静脉注射）在 SCID 小鼠的 BxPC-3 异种移植模型中观察体重肿瘤的生长并对肿瘤组织进行Western blot和免疫组化分析
结果：每周连续 5 天每天用 UMI-77 治疗两周，在第 19 天 和第 22 天 分别对肿瘤生长抑制了 65% 和 56%； 肿瘤组织裂解物的蛋白质印迹显示促凋亡蛋白 Bax 和 Bak 水平略有升高，存活素显着降低。[1]

Fluorescence polarization (FP)-based binding assays: Based on the Kd values, the concentrations of the proteins used in the competitive binding experiments are 90 nM for Mcl-1, 40 nM for Bcl-w, 50 nM for Bcl-xL, 60 nM for Bcl-2, and 4 nM for A1/Bfl-1. The fluorescent probes, Flu-BID and FAM-BID are fixed at 2 nM for all assays except for A1/Bfl-1 where FAMBID is used at 1 nM. 5 μL of the tested compound in DMSO and 120 μL of protein/probe complex in the assay buffer (100 mM potassium phosphate, pH 7.5; 100 μg/ml bovine gamma globulin; 0.02% sodium azide) are added to assay plates (Microfluor 2Black), incubated at room temperature for 3 h and the polarization values (mP) are measured at an excitation wavelength at 485 nm and an emission wavelength at 530 nm using the plate reader Synergy H1Hybrid. IC50 values are determined by nonlinear regression fitting of the competition curves.

Human pancreatic cancer cell lines AsPC-1, BxPC-3, and Capan-2 are cultured in RPMI-1640 medium, whereas Panc-1 and MiaPaCa are cultured in Dulbeccos' Modified Eagle's Medium (DMEM), all supplemented with 10% FBS. The cell growth inhibition after treatment with increasing concentrations of the compounds is determined by WST-8 assay.(Only for Reference)