Larry, I'm sure that others can add to this list, but off the top of my head, others that are focusing on the back-end (transcription factors) include ONCS, GNLB, KDUS? and a few on the front (kinases and phosphatases) are ARIA, SUGN, MLNM, CHIR. Of course the big pharmas also have programs through alliances with the above and others and they also have internal programs.
The transcription factors (intracellular hormone receptors, IRs, and STATs) are more advanced and pharmas have been targeting them even before they knew what they were because they focused on hormones and analogs. Thus, blockbuster products such as Premarin, Tamoxifen, Retin-A, Renova, Accutane, Rezulin, all target various IRs, so its a proven approach, although LGND is the only company to show synergy at the molecular level in an annimal model (Rexinoids which target RXRs synergizing with TZDs which target PPARs). Biotechs have products that target STAT pathways (and they have been targreting them before they knew what they were by focusing on interleukins, interferons, and growth factors) , but the proven products are at the very front end (polypeptide hormones that start the signal outside of the cell). These products include Epogen, Neupogen, Aldesleukin, Myotropin, Betaseron, etc. The small molecules that influence receptor/polypeptide hormone signalling have yet to be proven in advanced trials and I know of no combos (front and back end) that have been tried. |
