Temple University

Onconova Therapeutics, Inc.

Stephen Cosenza

E Premkumar Reddy

M V Ramana Reddy

Stanley Charles Bell

Glenn J Fegley

Jodie Duke

Reddy E Premkumar

Reddy M V Ramana

Activated cytotoxic compounds are described for attachment to targeting molecules for the treatment of a mammalian disease condition which comprise, an activator, a spacer linker, a linker (e.g., self-immolative), and a cytotoxic drug selected from the group consisting of AMINO-SUBSTITUTED (E)-2,6-DIALKOXYSTYRYL 4-SUBSTITUTED BENZYLSULFONES, AMINO-AND-HYDROXY SUBSTITUTED STYRYLSULFONANILIDES, and SUBSTITUTED PHENOXY- AND PHENYLTHIO-STYRYLSULFONE DERIVATIVES. Activated cytotoxic compound attached to a targeting molecule are described wherein the targeting molecule is selected from the group consisting essentially of an antibody, a receptor, a ligand, a cytokine, a hormone, and a signal transduction molecule. The invention is further directed to a method of treatment of disease conditions.

Activated cytotoxic compounds for attachment to targeting molecules for the treatment of mammalian disease conditions

Pre-treatment with &#x3b1;,&#x3b2; unsaturated aryl sulfones protects normal cells from the cytotoxic side effects of two classes of anticancer chemotherapeutics. Administration of a cytoprotective sulfone compound to a patient prior to anticancer chemotherapy with a mitotic phase cell cycle inhibitor or topoisomerase inhibitor reduces or eliminates the cytotoxic side effects of the anticancer agent on normal cells. The cytoprotective effect of the &#x3b1;,&#x3b2; unsaturated aryl sulfone allows the clinician to safely increasing the dosage of the anticancer chemotherapeutic.

Method for protecting normal cells from cytotoxicity of chemotherapeutic agents

Pre-treatment with &agr;,&bgr; unsaturated aryl sulfones protects normal cells from the cytotoxic side effects of two classes of anticancer chemotherapeutics. Administration of a cytoprotective sulfone compound to a patient prior to anticancer chemotherapy with a mitotic phase cell cycle inhibitor or topoisomerase inhibitor reduces or eliminates the cytotoxic side effects of the anticancer agent on normal cells. The cytoprotective effect of the &agr;,&bgr; unsaturated aryl sulfone allows the clinician to safely increasing the dosage of the anticancer chemotherapeutic.

Provided are the compound (E)-4-carboxystyryl-4-chlorobenzyl sulfone, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof.

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Voorhees, NJ, United States of America

Stephen Cosenza