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Telik Announces Presentation of New Data on the Characterization of Novel Ezatiostat (TELINTRA®, TLK199) Analogs at American Association for Cancer Research Annual Meeting
Date:4/5/2011

PALO ALTO, Calif., April 5, 2011 /PRNewswire/ -- Telik, Inc. (Nasdaq: TELK) today presented data at the 102nd American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida on a group of second generation analogs of ezatiostat, the most clinically advanced product in development at Telik.  Ezatiostat is the first inhibitor of glutathione-S-transferase P1-1 (GST P-1), a validated enzyme target in Myelodysplastic Syndrome (MDS), to successfully complete a Phase 2 clinical trial.  The efficacy and tolerability observed with ezatiostat in several Phase 1 and Phase 2 clinical trials supported the initiation of the analog program to identify potential follow-on drug candidates.  The structure-activity relationships for the most compelling of these analogs are presented in the AACR poster, entitled Synthesis and Biochemical Characterization of Novel Analogs of Ezatiostat Hydrochloride (TELINTRA®, TLK199) by Danying Cai et al.  A copy of the poster will be available on the Telik website at www.telik.com.

A series of diacid ezatiostat analogs bearing different substituents on the cysteinyl sulfur were synthesized using computer aided drug design and TRAP®, a proprietary drug discovery technology, to improve the inhibitory potency and selectivity for the target enzyme GST P1-1.  Substitutions resulted in a 30- to 130-fold improvement in in vitro potency against GST P1-1 and 3- to 10-fold higher selectivity relative to other isoforms.  

The analogs exhibited potent binding and inhibition of the drug target, GST P1-1, leading to activation of the signaling molecule Jun kinase.  Like ezatiostat, the analogs induced programmed cell death, or apoptosis, of human leukemia cells as well as the growth and differentiation of normal blood stem cells, lead
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