just incremental information .... and
in some cases maybe off topic ...
Our scientific founder, Timothy Haystead, Ph.D., currently at Duke University, utilized Serenex technology to identify the protein targets for geldanamycin, an anti-cancer natural product that was under development at the NCI, but stalled due to animal toxicity. First, the purine-binding proteome was reversibly captured on Serenex’s proprietary affinity media. Second, the media was eluted with increasing concentrations of geldanamycin. Analysis of the proteins competed away from the media by geldanamycin enabled us to identify the molecular targets for geldanamycin. In addition to the proposed therapeutic target, HSP90, a second target, ADE2, was eluted by the natural product. ADE2 was considered to be a potential toxicity target given its central role in purine biosynthesis. This hypothesis was tested by profiling a series of 62 geldanamycin analogs by the same process (Figure 4). This study led to the identification of compounds that were selective for either HSP90 or ADE2. Analogs that were selective for HSP90 retained anti-tumor activity but displayed reduced general toxicity, thus validating the hypothesis of ADE2 as a toxicity target. Based on these findings, new compounds were selected for development by the NCI, and in early 2003 this family of potential drugs was licensed to Kosan Biosciences.
See page 3
serenex.com
CELL. MOL. BIOL. LETT. Vol. 8. No. 2A. 2003
INHIBITION OF HSP90 AS A SPECIAL WAY TO INHIBIT PROTEIN
KINASES
PETER CSERMELY and CSABA SOTI
Department of Medical Chemistry, Semmelweis University, Budapest 8, Hungary
cmbl.org.pl
Sloan-Kettering
mskcc.org
Three-way collaboration to identify and develop inhibitors of the HSP90 chaperone proteins as potential anti-cancer drugs
laboratorytalk.com
Scientists Find Protein at the Intersection of Genetics, Development, and the Environment
wi.mit.edu
The web site of the International conferences on
"The Hsp90 chaperone machine"
unige.ch
Luke Whitesell, M.D.
Associate Professor,
Pediatric Hematology/Oncology
Mail: Arizona Health Sciences 5341
P.O. Box 245073
Tucson AZ 85724-5073
Phone: 520/626-4851
Fax: 520/626-6986
e-mail: whitelj@peds.arizona.edu
Summary of Research Activities
Targeting Heat Shock Proteins to Treat Cancer
azcc.arizona.edu
Press Releases
CONFORMA THERAPEUTICS CORPORATION CLOSES $30 MILLION FINANCING
SAN DIEGO, CA - September 18, 2003 -- Conforma conformacorp.com
John McCarthy |
