University System of Maryland

Cornell University

Donald J Creighton

Diana S Hamilton

Bruce Ganem

Zhe-Bin Zheng

Zhebo Ding

Malcolm J Kavarana

Compounds comprising two human GlxI inhibitors covalently linked via a chemical linker are provided, wherein each of said two human GlxI inhibitors, which may be the same or different, is an S-substituted glutathione or an S-substituted glutathione prodrug, wherein said GlxI inhibitors each have a &#x3b3;-glutamyl amino group, wherein said chemical linker is covalently bound to each GlxI inhibitor via said &#x3b3;-glutamyl amino group, and wherein said chemical linker has a length of at least 50 Angstroms. Monovalent irreversible inactivators of human GlxI are also provided. An antineoplastic composition is provided, which comprises a compound described above and a pharmaceutically acceptable carrier. In vitro and in vivo methods of preventing or inhibiting the growth and proliferation of neoplastic cells and/or tumors are also provided.

Inactivators and bivalent inhibitors of glyoxalase I and methods of inhibiting tumor growth

Described herein are new enone derivatives and conjugates. Additionally, methods for synthesizing these new enones are also disclosed. These compounds can be employed in cancer therapy.

Enone cancer therapeutics

The present invention provides a compound having the structure ##STR1## wherein S* is S.dbd.O or O.dbd.S.dbd.O; and wherein R.sub.1 is selected from the group consisting of (C.sub.1 -C.sub.9) alkyl, (C.sub.3 -C.sub.8) cycloalkyl, (C.sub.5 -C.sub.7) cycloalkenyl, and (C.sub.6 -C.sub.20) aryl substituted with halogen or (C.sub.1 -C.sub.18) alkyl; and wherein R.sub.2 is selected from the group consisting of alkyl, (C.sub.1 -C.sub.9) alkyl, (C.sub.3 -C.sub.8) cycloalkyl, (C.sub.5 -C.sub.7) cycloalkenyl, and (C.sub.6 -C.sub.20) aryl substituted with halogen or (C.sub.1 -C.sub.18) alkyl. Also provided are various methods of using the compositions of the present invention.

Competitive inhibitors of glyoxalase I and method of generating such

A compound of the formula ##STR1## with R being hydrogen, alkyl, cycloalkyl or aryl, which may be substituted with halogen or alkyl, and R' and R.sup.a being hydroxyl, or --O-alkyl, pharmaceutically acceptable salts thereof; or mixtures thereof. An anti-neoplastic composition comprises the compound described above and a pharmaceutically acceptable carrier. In vitro and in vivo methods of preventing or inhibiting the growth and proliferation of neoplastic cells and/or tumors comprise contacting the cells with or administering to a subject an anti-growth and proliferation effective amount of the compound described above.

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Baltimore, MD, United States of America

Donald J Creighton