Chemical binding compounds can effectively inhibit the function of target proteins that possess “ideal binding pockets”. This type of targets accounts only less than 20% of possible disease targets, with the remaining 80% called “undruggable targets”. To hit these “undruggable targets” new methods and novel modalities have been developed. Among these are target degradation methods and covalent bonding modalities. At Polymed we deploy these new approaches for cancer and other disease targets.

Protein Degradation Technologies

Proteolysis targeting chimera, or PROTAC is an approach aimed at sending the target protein for proteasome degradation relying on PROTAC molecule-induced complex formation between the target and appropriate E3 ubiquitin ligase and subsequent ubiquitination of the target protein. Currently, the Polymed team is refining the technique and applying it to certain cancer or autoimmune disease targets.

In addition to ubiquitination/proteasome pathway for protein degradation, other intrinsic cellular protein degradation phenomena are also studied by various academic laboratories. The Polymed team is actively engaging in collaborations to explore novel therapeutic applications of these protein degradation pathways.

HPB-001 Project

Although the target for HPB-001 was found as the oncogenic driver in many cancers, its unique allosteric structure under physiological conditions makes it unsuitable for conventional chemical inhibitors. Recently, an alternative inhibitor approach was successfully applied to a mutant form of the target. We view attempts along this line of thinking as successful clinical target validation by deployment of chemical biology for drug discovery. We are using artificial intelligence to design molecules with best fit for more mutations of this important oncology target in order to develop novel PROTAC molecules.

HPB-002 Project

A signaling complex is often comprised with a key molecule with multiple functions, and the target for HPB-002 is such a molecule which functions with its protein kinase activity while providing a scaffold for the assembly of signal transduction complex. So far the approaches for merely inhibiting its kinase activity have not been very successful in treating autoimmune/inflammation conditions. We are developing PROTAC molecules against this target in order to completely suppress its dual functions.

Protein Kinase Inhibitor

Phosphorylation catalyzed by various protein kinases is a key phenomenon for regulation of many cellular processes and pathophysiology. Polymed carries out advanced research to discover best-in-class molecules against key targets for treating autoimmune diseases and cancer.

HPB-003

The target for HPB-003 belongs to a subfamily of protein tyrosine kinases. These subfamily members transduce signals of many interleukins and growth factors with certain overlapping functionality. The therapeutic concept for HPB-003 is to identify molecules with unique inhibitory profile against different subfamily members in order to achieve maximal anti-inflammation effect while avoiding unwanted anti-hematopoiesis effects.