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, leading to the acceleration of recovery of neutrophil levels in preclinical models of chemotherapy-induced neutropenia. Further investigation of the most potent and selective analogs in biochemical and cellular assays is underway to assess their potential as clinical development candidates for the treatment of hematologic malignancies.
Select the service that is right for you!COMPARE ALL SERVICES
Jim Cramer and Stephanie Link actively manage a real portfolio and reveal their money management tactics while giving advanced notice before every trade.
- $2.5+ million portfolio
- Large-cap and dividend focus
- Intraday trade alerts from Cramer
- Weekly roundups
Access the tool that DOMINATES the Russell 2000 and the S&P 500.
- Buy, hold, or sell recommendations for over 4,300 stocks
- Unlimited research reports on your favorite stocks
- A custom stock screener
- Upgrade/downgrade alerts
Jim Cramer's protege, David Peltier, identifies the best of breed dividend stocks that will pay a reliable AND significant income stream.
- Diversified model portfolio of dividend stocks
- Alerts when market news affect the portfolio
- Bi-weekly updates with exact steps to take - BUY, HOLD, SELL
All of Real Money, plus 15 more of Wall Street's sharpest minds delivering actionable trading ideas, a comprehensive look at the market, and fundamental and technical analysis.
- Real Money + Doug Kass Plus 15 more Wall Street Pros
- Intraday commentary & news
- Ultra-actionable trading ideas
Our options trading pros provide daily market commentary and over 100 monthly option trading ideas and strategies to help you become a well-seasoned trader.
- 100+ monthly options trading ideas
- Actionable options commentary & news
- Real-time trading community
- Options TV