product pipeline
Using both experimental and in silico library screening techniques, PHusis has identified a novel class of non–lipid small molecules that bind selectively to the PH-domain of different classes of PH-domain signaling proteins.
Binding affinities for each target PH-domain are acquired experimentally using Surface Plasmon Resonance (SPR) spectroscopy. Agents are evaluated in vitro for efficacy and the leads are iteratively refined through molecular modeling using PHuDock® and binding by SPR spectroscopy.
The lead program has identified a selective inhibitor of PDK1, PHT-427 which has shown excellent in vivo antitumor activity against human tumor xenografts with activated EGFR/PI3-kinase pathways signaling, and in a metastatic melanoma model with mutant NRAS that provides resistance against the mutant BRAF inhibitor vemurafenib.
Lead optimization is underway in PHusis’ second program for highly selective inhibitors of mutant KRAS along with the development of an accompanying biomarker assay that will identify patients with cancers addicted to mut-KRAS signaling.
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