About PHusis Therapeutics

PHusis is designing precision medicines using its proprietary computational modeling platform, PHuDock to rapidly identify inhibitors of proteins with regulatory PH-domains that drive cancer growth. The approach provides PHusis with the means of identifying drug leads more rapidly and in a cost effective manner. The result is, PHusis has built a pipeline of drug leads against some novel and critical cancer targets including PDK1, mutant KRAS and NRAS. Patients can be selected for treatment based on their mutational profile, eliminating unnecessary treatment of patients without the targets.

There is an urgent unmet need for innovative approaches to the development of more effective and safer molecular targeted therapeutics. To address this need, PHusis Therapeutics Inc. is using its proprietary integrated high-throughput computational molecular docking platform, PHuDock®, installed in our high-performance computing cluster; in combination with the Schrödinger suite. These are coupled to large chemical and biological databases to conduct computationally intensive high-throughput docking and ligand-based virtual screening in order to discover and develop anticancer inhibitors. Our main targets are a class of novel membranephosphoinositide lipid binding pleckstrin homology (PH)-domain proteins found in a number of important signaling proteins relevant to cancer.

The use of the PH-domain as a drug target represents a paradigm shift in the approach to cancer drug development that has traditionally focused on inhibiting catalytic activity or ligand binding. PHusis small molecules PH-domain inhibitors are differentiated from the multitude of kinase inhibitors through their improved toxicity profiles and the targeting of conventionally “undruggble” targets. Our two lead drug candidates target the largest cancer markets with unmet needs lung and colon cancer

Using PHuDock®, X-Ray structural information and Surface Plasmon Resonance (SPR) spectroscopic measurements of selected drug-like molecules, PHusis has been able to rapidly and efficiently identify agents that selectively inhibit the activity of a number of these cancer driving proteins. Importantly, this is achieved without the toxicity often associated with cancer drugs. PHuDock® has been applied to lead identification and optimization, as well as to predict the compounds off-target properties and toxicity, therefore delivering novel and highly effective agents with low toxicity.  

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PHusis has built a pipeline of drug leads against some unique cancer targets including PDK1 for mutant NRAS melanoma, and CNKSR1 and PLEK for mutant KRAS in lung and colon cancer,  Further refinement and optimizations of these leads will provide agents that will be rapidly advanced through IND enabling studies to clinical trials. PHusis’ first drug candidate, the PDK1 inhibitor PHT-427 has entered IND-enabling preclinical development.

PHT-427 compound

PHusis PDK1 inhibitor PHT- 427 (cyan) and the co-crystallized IP4 (green core) from the high resolution structure of the PH-domain showing the striking overlay of the sulphonamide portion of PHT-427 and the phosphate group of IP4.