Preclinical evaluation of novel selective HDAC6 inhibitors for human cancers treatment

Background: In this project, we will develop the preclinical animal studies of azaaryl-based HDAC6 inhibitors to be anticancer candidate drug. According to our data, MPT0G211 and MPT0G211 mesylate showed significantly higher potency than ACY-1215 and tubastatin, which were known as HDAC6 inhibitors, in selectivity and inhibition of HDAC6 activity. MPT0G211 and its salt form MPT0G211 mesylate showed tumor suppression in nude mice bearing human multiple cancer cells xenografts. In conclusion, MPT0G211 and MPT0G211 mesylate exhibited satisfactory therapeutic effects in human cancers. Purpose: This project aims to complete the preclinical animal studies, including in vivo pharmacological efficacy and toxicity, of HDAC6 inhibitors toward anticancer drug candidate. Method: Goals will be achieved in following aspects: (1) efficacy evaluation with pharmacodynamic functions in human hematologic and solid tumor xenograft models using combination treatments. (2) toxicity/safety studies and dose finding by preclinical studies which will be tested by outsourcing. Anticipated results: Taken all results together, we should be able to identify a most promising compound as a new drug candidate, and transfer this project to a biotechnological company for further drug development of Industry-Academic Cooperation and Investigational New Drug (IND) application.