Myeloid cell leukemia-1 (Mcl-1) is a potent anti-apoptotic protein and a member of the pro-survival Bcl-2 family. UMI-77 is a selective Mcl-1 inhibitor with a Ki value of 490 nM and exhibits selectivity over other members of the Bcl-2 family (Kis = 5.3, 23.8, 33.0, and 8.2 μM) for A1/Bfl-1, Bcl-2, Bcl-xL, and Bcl-W, respectively). It has been shown to disrupt the heterodimerization of Mcl-1/Bax and Mcl-1/Bak, thus antagonizing Mcl-1 function. UMI-77 inhibits the growth of various pancreatic cancer cell lines with IC50s values ranging from 3.4-16.1 μM, inducing apoptosis through activation of the intrinsic apoptotic pathway and/or Bax conformational change. In a BxPC-3 xenograft mouse model, 60 mg/kg UMI-77 demonstrated antitumor activity without damaging normal tissues.
