Date: 2015-04-20
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the American Association for Cancer Research (AACR)
Company: Mission Therapeutics (UK)
Product: UCHL1 inhibitors
Action mechanism:
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 20, 2015, Mission Therapeutics, a company focused on the discovery and development of modulators of the deubiquitylating (DUB) enzyme family for the treatment of cancer and other diseases, has presented a poster at AACR entitled “Discovery of highly selective UCHL1 inhibitors with in vivo pre-clinical anti-tumour activity”. UCHL1 is a prototypical oncogene that selectively drives proliferation in many tumour types including multiple myeloma and lung cancer. UCHL1 depletion leads to the selective killing of a number of tumours whose proliferation is driven by UCHL1. Validation of DUB targets like UCHL1 exemplifies the rationale for developing inhibitors of the ubiquitin pathways to target a broad range of cancers with defined genetic abnormalities, or resistance to standard-of-care modalities. Using its integrated drug discovery platform combining unique biochemical, cellular, biophysical and structural assays, Mission has identified and optimised potent and selective small molecule, active site inhibitors of UCHL1. These inhibitors recapitulate UCHL1 target biology and exhibit in vitro target engagement in proprietary cellular assays. Further lead optimisation has generated compounds with drug-like properties that demonstrate efficacy in disease models. Cumulatively, the data support not only the potential further pre-clinical development of UCHL1 compounds but also the tractability of a broader range of DUBs to pharmacologic intervention, with the potential to reach a diversity of cancers comprising different genetic signatures.
