Contact Us
Research
Castration-resistant prostate cancer (CRPC) is incurable and new therapeutic approaches are essential and are desperately sought after, particularly for metastatic CRPC, which has a dismal 30% 5-year survival rate. Arginine vasopressin receptor type 1a (AVPR1A), a G protein-coupled receptor, was discovered to be a promising therapeutic target for CRPC including late-stage bone metastatic disease (Zhao et al. Science Translational Medicine 2019). We are actively developing highly selective (including isoform selectivity against AVPR1b and AVPR2), highly potent, and orally bioavailable AVPR1a antagonists hoping to find novel therapeutics for treating CRPC.
One major focus of drug discovery in Dr. Feng’s lab is the development of viable STK17A inhibitors. STK17A (serine/threonine kinase 17a) is a cytoplasmic serine/threonine kinase. It is a member of the death‑associated protein kinase (DAPK) family and plays a significant role in cell proliferation, apoptosis, tumor metastasis and tumorigenesis. Thus, inhibition of STK17A can find wide anti-cancer applications, such as the treatment of leukemia, lung cancer, breast cancer, ovarian cancer, gastric cancer, oral cancer, head and neck cancer, myeloma, medulloblastoma, and glioblastoma, etc. We are developing three types of STK17A inhibitors: (1) orally bioavailable and highly selective STK17A inhibitors for treating various peripheral cancers; (2) brain penetrant STK17A inhibitors for treating brain tumors, particularly glioblastoma (GBM); and (3) STK17A degraders or Protac compounds based on novel STK17A modulators developed in-house.
Targeting Bruton’s tyrosine kinase (BTK) is an effective way for treating multiple B-cell malignancies. Thus far, both covalent and non-covalent BTK inhibitor drugs have been developed and are in clinical uses, but patients discontinue these agents due to resistance and intolerance. The resistance is mainly caused by mutations. We hypothesize that novel chemical structures that bind to BTK in a different manner than previously developed inhibitors, as well as those that target alternate pathways, can be used to overcome BTK inhibitor resistance. We are actively developing novel chemotypes/compounds (including Protac compounds) that are effective for inhibiting mutated BTKs.
Inhibition of the cyclin-G associated kinase (GAK) is a novel way for treating diffuse large B-cell lymphoma (DLBCL). GAK carries out alignment of the machinery that pulls chromosomes apart during cell division, and a GAK inhibitor halts the cell division and promotes programmed cell death (apoptosis). One advantage of inhibiting GAK is that it attacks the tumors while sparing the normal blood cells. We are developing both covalent and non-covalent GAK inhibitors to find novel drugs that can effectively treat DLBCL. In addition, GAK degraders (Protac compounds) will also be pursued, which are derived from the proprietary GAK inhibitors developed in-house.