San Diego, CA, September 07, 2013 --(PR.com
)-- Jean Cui, Associate Research Fellow of Oncology Medicinal Chemistry at Pfizer will give a presentation on “Lessons from PF-04254644, an Inhibitor of Receptor Tyrosine Kinase c-Met with High Protein Kinase Selectivity, but Broad Phosphodiesterase Family Inhibition Leading to Myocardial Degeneration in Rats” at the 2nd Protein Kinases & Drug Design Conference to be held in San Diego, CA on October 24-25, 2013 by GTC.
The HGF/c-Met signaling axis is deregulated in many cancers and plays important roles in tumor invasive growth and metastasis. Exclusively selective c-Met inhibitor (S)-6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (PF-04254644) was discovered from a highly selective HTS hit via structure based drug design and medicinal chemistry lead optimization. PF-04254644 had many attractive properties meriting preclinical evaluation. Broad off-target screens identified PF-04254644 as a pan-PDE family inhibitor which was implicated in a sustained increase in heart rate, increased cardiac output, and decreased contractility indices, as well as myocardial degeneration in in vivo safety evaluations in rats. PF-04254644 was terminated as a preclinical candidate because of a narrow therapeutic window in cardio-related safety. The learning from multi-parameter lead optimization and strategies to avoid the toxicity attrition at the late stage of drug discovery will be discussed.
Kinases, key drivers of malignant transformation and major contributors to a variety of other human pathologies, have emerged as some of the most exciting targets in drug discovery. However, with initial well documented success stories came realization that many hurdles lie in the path of successful development of new drugs, targeting kinase signaling. GTC’s 2nd Protein Kinases & Drug Design Conference will bring together speakers representing world leading academic centers and pharmaceutical companies to discuss how to overcome the many hurdles and answer exciting key questions.
This conference is part of our Protein Discovery Summit 2013, which includes three additional parallel conferences shown below:
Protein Kinases & Drug Design
Antibody & Protein Therapeutics
Protein Expression, Purification & Characterization
For more information, please visit www.gtcbio.com