1. Academic Validation
  2. 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

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

  • J Med Chem. 2011 Sep 22;54(18):6254-76. doi: 10.1021/jm200570p.
M V Ramana Reddy 1 Padmavathi Venkatapuram Muralidhar R Mallireddigari Venkat R Pallela Stephen C Cosenza Kimberly A Robell Balaiah Akula Benjamin S Hoffman E Premkumar Reddy
Affiliations

Affiliation

  • 1 Department of Oncological Sciences, Icahn Medical Institute, Mount Sinai School of Medicine, New York, New York 10029-6514, USA. r.reddy@mssm.edu
Abstract

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

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