Vasiliou, Vasilis (University of Colorado Denver)
Simeonov, Anton (NCATS)
Jadhav, Ajit (NCATS)
Maloney, David (NCATS)
Yasgar, Adam (NCATS)
Lal, Madhu (NCATS)
Chen, Ying (University of Colorado Denver)
Miller, Bettina (University of Colorado Denver)
Messersmith, Wells (University of Colorado Denver)
Arcaroli, John (University of Colorado Denver)
Jimeno, Antonio (The Regents of the University of Colorado, A Body Corporate)
Thompson, David (The Regents of the University of Colorado, A Body Corporate)
This technology includes the identification and use of novel inhibitors of ALDH1A1 (aldehyde dehydrogenase 1 family member A1) for the treatment of multiple diseases, including cancer, inflammation, and obesity. ALDH1A1 is an enzyme that has a role in alcohol metabolism, and has been implicated in maintaining cancer stem cells. A high-throughput screen was conducted that identified novel ALDH1A1 inhibitors. Medicinal chemistry optimization led to the identification of two chemical series with high potency, selectivity, and favorable ADME (absorption, distribution, metabolism, and excretion) properties.
Further clinical work with the novel inhibitors could support the indication of these novel ALDH1A1 inhibitors for a variety of indications including but not limited to cancer, inflammation, and obesity.
The compounds of this series represent the most potent, selective, and drug-like inhibitors of ALDH1A 1 described to date.