Selection of a Water-Soluble Salt Form of a Preclinical Candidate, IIIM-290: Multiwell-Plate Salt Screening and Characterization.

ABSTRACT: IIIM-290, a semisynthetic derivative of natural product rohitukine, is an orally bioavailable Cdk inhibitor, efficacious in the xenograft models of colon, pancreatic, and leukemia cancer. Its low aqueous solubility (∼8.6 μg/mL) could be one of the reasons for achieving optimal in vivo efficacy relatively at a higher dose. Being a nitrogenous compound, salt formation was envisaged as one of the ideal approaches to enhance its solubility and dissolution profile. Thus, herein, a solubility-guided miniaturized 96-well plate salt screening protocol was devised for identification of the suitable salt form of this preclinical candidate. The solubility-guided strategy has resulted in the identification of hydrochloride as the most favorable counterion, resulting in 45-fold improvement in aqueous s

SUBMITTER: Kumar V 

PROVIDER: S-EPMC6072253 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature