KINASE POTENCY AND SELECTIVITY
In humans, more than 518 kinases mediate cellular signaling pathways that are involved in critical physiological functions in our body, such as replenishing of new cells (cell proliferation) and removal of unwanted cells (programed cell death or apoptosis). Kinases also play a major role in our immune system by transducing signals from the cell surface to the cell nucleus, which directs the cell’s response to an external stimulus. Aberrant kinase signaling is known to be a leading factor involved in many cancers, immune disorders and other diseases. Kinase inhibitors are effective drugs for treating cancers and over fifty kinase inhibitors have now been approved for oncology indications. However, most approved kinase inhibitors display low selectivity and hit many kinases simultaneously, thus leading to undesirable toxicity and adverse effects. Challenges remain to develop kinase inhibitors that are both highly selective and highly potent, to achieve better patient safety and higher therapeutic efficacy. Snap Bio’s technology platform is designed to overcome these challenges and this platform has been validated through our preclinical candidate SNP-162, which displays high kinase selectivity (see below) and potency (pM-low nM). SNP-162 also is highly active against a range of cancer cells, including liver cancer cell lines such as HepG2, Hep3B and Huh7.
Cancer cells often alter normal cellular signaling pathways to promote uncontrolled tumor growth through stimulation of cell proliferation and activation of cell survival mechanisms. The rapid proliferation of cancer cells enables a high frequency of genetic mutations that often leads to cancer drug resistance. For example, Sorafenib (Nexavar) resistance in liver cancer patients is acquired rapidly, which limits the effectiveness of this first-line therapy. Snap Bio is taking a genetic marker-driven approach to overcome cancer drug resistance. This approach has been validated through our lead program involving highly potent and selective kinase inhibitors that disrupt multiple genetically-defined cancer growth and survival pathways. Our molecules inhibit different growth and proliferation pathways relative to FDA-approved drugs, Sorafenib and Regorafenib (Stivarga), for advanced liver cancer and we have demonstrated strong synergistic effects to halt cancer cell growth when used in combination.