Potent TMEM16A Small Molecule Treatment for Inflammatory and Reactive Airway Diseases, Asthma, Hypertension, Pain and Cancer
Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a Ca2+-activated Cl- channel expressed widely in mammalian epithelia, vascular smooth muscle and electrically excitable cells. Increased TMEM16A expression is associated with COPD and asthma, and TMEM16A is reported as a biomarker for gastrointestinal stromal and esophageal tumors. Pharmacological TMEM16A inhibitors, including the AACT small molecule scaffolds described in this invention, could be used to treat diseases such as inflammatory and reactive airway diseases, hypertension, gastrointestinal hypermotility and some cancers. The TMEM16A inhibitors developed by UCSF scientists have the following advantages: IC50 ~ 30 nM; substantially more potent than prior compoundsSubstantially better metabolic stability and PK than prior compoundsDemonstrated efficacy in acute hypertension, inhibition of intestinal smooth muscle contraction and inhibition of GI tumor cell growth
The Verkman lab at the University of California, San Francisco has discovered, synthesized and biochemically evaluated of a series of TMEM16A inhibitors. The chemical structure of the 2-acylamino-cycloalkylthiophene-3-carboxylic acid arylamide inhibitor scaffold was refined through medicinal chemistry to identify bromodifluoroacetamide-based inhibitors with enhanced potency and metabolic stability.
Stage of Development Proof of Concept – in vitro and ex vivo Looking for Partners To develop & commercialize the TMEM16A inhibitors as therapies for inflammatory and reactive airway diseases, hypertension, gastrointestinal hypermotility and some cancers. Data Availability Under NCD/CDA Related Materials Additional Technologies by these Inventors Tech ID/UC Case 29236/2017-138-0 Related Cases 2017-138-0
USA
