UMI-77, a specific Mcl-1 inhibitor (Ki: 490 nM), has selectivity over other members of Bcl-2 family.

MCL1:490 nM(Ki)

UMI-77（60 mg/kg, i.v. ）在BxPC-3异种移植小鼠模型中具有单剂量抗肿瘤活性且不损害正常组织

UMI-77可激活固有的凋亡通路和/或Bax构象改变,从而促使胰腺癌细胞凋亡。UMI-77可干扰细胞 Mcl-1和BL-Noxa间的相互作用,还干扰Mcl-1/Bax蛋白-蛋白相互作用。UMI-77抑制胰腺癌细胞的生长,如BxPC-3,Panc-1,MiaPaCa-2,AsPC-1 和 Capan-2细胞（IC50：3.4/4.4/12.5/16.1/5.5 μM）。

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)