Telik Presents Preclinical Data at 99th Annual Meeting of theAmerican Association for Cancer Research
PALO ALTO, Calif., April 17, 2008 /PRNewswire-FirstCall/ -- Telik, Inc. , a biopharmaceutical company focused on discovering and developing drugs to treat serious diseases, today announced that it made four preclinical data presentations at the 99th Annual Meeting of the American Association for Cancer Research (AACR) in San Diego, Calif. The abstracts highlighted results from Telik's Research and Development programs.
Identification and Characterization of Novel Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor 2 [Abstract # 1439]
Inhibition of the vascular endothelial growth factor receptor signaling pathway with antibodies or small molecules has been proven effective as an anti-cancer therapy. Through the use of Telik's Target-Related Affinity Profiling (TRAP(R)) screening technology, novel inhibitors of VEGFR2 kinase were discovered. The inhibitors belong to nine structural classes, among which E2B8 and EAAF are sub-micromolar inhibitors of the kinase.
Mechanism of Induction of Apoptosis by TLK199 (TELINTRA(R)) in Human Leukemia Cell Lines [Abstract # 2270]
Telik researchers conducted studies with data highlighting TLK199, a novel glutathione analog inhibitor of the enzyme glutathione S-transferase P1-1, which induces apoptosis, or programmed cell death, in human HL60 promyelocytic cells and TF-1 erythroleukemic cells. Treatment of the leukemia cells with TLK199 also resulted in an increase of the phosphorylation of eIF2alpha, a key signaling event in the integrated stress response (ISR), and in induction of multiple genes implicated in ISR. Telik currently has ongoing studies of TLK199 in clinical development for the treatment of myelodysplastic syndrome (MDS).
Identification of a Novel Class of Nonpeptidyl Small-Molecule Inhibitors of the Human Proteasome [Abstract # 3271]
The ubiquitin-proteasome system (UPS) mediated protein turnover underlies many signaling pathways that are fundamental to cell proliferation, survival and death. Many important cellular proteins that are dysregulated in cancer are proteasome substrates. Telik researchers have identified multiple nonpeptidyl small-molecule hits that inhibited human proteasome activity both biochemically and in cells. The best series exhibited many desirable features including excellent cellular specificity, equal activity against all three proteolytic sites of the proteasome, and potent and broad anti-tumor activity in vitro.
Target-Related Affinity Profiling (TRAP(R)): Efficient Cancer Drug Discovery at Telik [Abstract # 4754]
Compounds for these preclinical studies came through the use of Telik's TRAP technology, which provides an alternative screening method that is based on a unique molecular descriptor called an affinity fingerprint. An affinity fingerprint is based on the binding energy of small molecules to proteins. Advanced computational methods are used to determine affinity fingerprints, and to select compounds for screening. Advantages to using TRAP include: a "low throughput" approach using complex, physiologically relevant assays; identification of small molecule drug leads after testing as few as 200 compounds; high level of success against a wide range of cancer targets; enables scaffold hopping; and can speed the optimization of small molecule drugs.
Telik, Inc. of Palo Alto, CA, is a biopharmaceutical company focused on discovering, developing and commercializing novel small molecule drugs to treat serious diseases. The company's most advanced investigational drug candidates in clinical development are TELINTRA, a modified glutathione analog for the treatment of cytopenias due to myelodysplastic syndrome or chemotherapy, and TELCYTA(R), a tumor-activated prodrug for the treatment of advanced ovarian cancer and non-small cell lung cancer. Telik's product candidates were discovered using its proprietary drug discovery technology, TRAP, which enables the rapid and efficient discovery of small molecule drug candidates.
TELIK, the Telik logo, TELCYTA, TELINTRA and TRAP are trademarks or registered trademarks of Telik, Inc.
Posted: April 2008