Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (E)-2-{2-Methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): Synthesis, Structure–Activity Relationship, and Biological Activity

• DOI: 10.1021/jm200570p
• Publication Date: 2011-08-03T16:55:38Z
• Authors: M. V. Ramana Reddy; Padmavathi Venkat...; Muralidhar R. Mal...; Venkat R. Pallela; Stephen C. Cosenza; Kimberly A. Robell; Balaiah Akula; Benjamin S. Hoffman; E. Premkumar Reddy
• Keywords: Sodium acetate; Structure–activity relationship

Cyclin D proteins are elevated in many cancer cells, and targeted deletion of cyclin D1 gene the mammary tissues protects mice from breast cancer. Accordingly, there is an increasing awareness this novel nonenzymatic target for therapeutics. We have developed novel, nonalkylating styrylbenzylsulfones that induce cell death wide variety cells without affecting proliferation survival normal cells. The development derivatized followed logically a tumor cytotoxicity screen performed our laboratory did not priori profile. Modifications some precursor molecules led to lead optimization with regard cytotoxicity. In report we describe synthesis structure-activity relationships (E)-styrylbenzylsulfones anticancer agent sodium (E)-2-{2-methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na), which phase III trials myelodysplastic syndromes (MDS) associated aberrant expression proteins.