Introduction: Myeloid leukemia 1 (Mcl-1), an antiapoptotic protein of the Bcl-2 family, is an attractive target for cancer therapy. In recent years, significant progress has been made with regard to Mcl-1 inhibitors, leading to the generation of highly potent Mcl-1 inhibitors that have entered clinical trials.
Areas covered: This review provides an overview of the patent literature between 2020 and 2022 -covering inhibitors, antibody-drug conjugate (ADC), and proteolysis targeting chimera (PROTAC) of Mcl1.
Expert opinion: Despite the great success of Mcl-1 inhibitor development, the on-target toxicity to heart indicated that the BH3 mimetic Mcl-1 inhibitors could have a limited therapeutic window.Drug combinations of Mcl-1 inhibitors with targeted therapies or chemotherapies may improve safety as they may reduce the dose of Mcl-1 inhibitors. Alternatively, some technologies like ADC and PROTACS could also be utilized to improve the therapeutic window. We envision a precision medicine platform like BH3 profiling or single-molecule pull-down and co-immunoprecipitation platform will enable the tailored use of Mcl-1 inhibitors utilizing the unique molecular information of individual patients.
Keywords: BH3 mimetic; Bcl-2; Mcl-1; anticancer; small molecule inhibitors.