The University of Texas System

Joyant Pharmaceuticals, Inc.

Lin Li

Hidetaka Suzuki

Xiaodong Wang

Jef K. De Brabander

Patrick G. Harran

Ranny Mathew Thomas

Patrick G Harran

Gunnar J Hanson

Jef K De Brabander

Charles G Caldwell

Ming Zhou

Qi Wei

Susan Harran

Jing Li

Susan Jeong

Jef K DeBrabander

Gelin Wang

Noelle Williams

Anthony Burgett

Caspase activity and apoptosis are promoted using active, dimeric Smac peptide mimetics of the general formula M1-L-M2, wherein moieties M1 and M2 are monomeric Smac mimetics and L is a covalent linker. Target cancerous or inflammatory cells are contacted with an effective amount of an active, dimeric Smac mimetic, and a resultant increase in apoptosis of the target cells is detected. The contacting step may be effected by administering to a pharmaceutical composition comprising a therapeutically effective amount of The compoundic mimetic, wherein the individual may be subject to concurrent or antecedent radiation or chemotherapy for treatment of a neoproliferative pathology.

Dimeric small molecule potentiators of apoptosis

This invention relates to novel macrocyclic lactams intermediates useful for the preparation of diazonamide analogs. This invention also relates to a novel electrochemical oxidative cyclization for the preparation of such macrocyclic lactams, and their further elucidation to provide diazonamide analogs.

Methods for preparing diazonamides

Caspase activity and apoptosis are promoted using active, dimeric Smac peptide mimetics of the general formula M1-L-M2, wherein moieties M1 and M2 are monomeric Smac mimetics and L is a covalent linker. Target cancerous or inflammatory cells are contacted with an effective amount of an active, dimeric Smac mimetic, and a resultant increase in apoptosis of the target cells is detected. The contacting step may be effected by administering to a pharmaceutical composition comprising a therapeutically effective amount of the dimeric mimetic, wherein the individual may be subject to concurrent or antecedent radiation or chemotherapy for treatment of a neoproliferative pathology.

Ornithine &#x3b4;-aminotransferase (OAT) facilitates microtubule assembly in addition to its aminotransferase activity in mitochondria. An N-terminal proteolysis of the first 17 amino acids of OAT block its transport to the mitochondria. The resultant truncated protein (OATC) forms specific complexes with mitotic spindle promoting proteins such as Eg5 and takes on a Ran-dependent spindle-assembly activity. Methods and compositions for inhibiting mitotic spindle assembly in a cell by specifically inhibiting OAT, and methods for screening for inhibitors of (1) the spindle-assembly function of OAT, (2) the protease that N-truncates OAT, (3) the OAT/RanGTP association and (4) the OAT/Eg5 association are disclosed.

Ornithine aminotransferase (OAT): a target for anticancer drugs

A specific diazonamide A analog and its salts and conjugates are effective in treating proliferative diseases.

Diazonamide A analog

The application discloses novel synthetic compounds, modeled after unique toxins extracted from the marine invertebrateuseful in the treatment abnormal cell mitosis. The application also discloses novel methods for synthesis of these compounds and methods of using these compounds.

Synthetic diazonamides

Synthetic diazonamides as novel anti-mitotic agents

Growing community of inventors

Dallas, TX, United States of America

Patrick G Harran