Technology Bundle ID

Small Molecule Inhibitors of Lactate Dehydrogenase as an Anti-Cancer Therapy

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Lead Inventors
David Maloney (NCATS)
Ajit Jadhav (NCATS)
Alex Waterson (Vanderbilt University)
Anton Simeonov (NCATS)
Bryan Mott (NCATS)
Chi Dang (The University of Pennsylvania)
Daniel Urban (NCATS)
Ganesha Rai Bantukallu (NCATS)
Gary Sulikowski (Vanderbilt University)
Jennifer Kouznetsova (NCATS)
Kwangho Kim (Vanderbilt University)
Kyle Brimacombe (NCATS)
Leonard Neckers (NCI)
Plamen Christov (Vanderbilt University)
Shyh Yang (NCATS)
Somnath Jana (Vanderbilt University)
Victor Darley-Usmar (University of Alabama @ Birmingham)
William Moore (NCI)
Xin Hu (NCATS)
This technology includes a novel pyrazole-based compound NCGC00274266 (MLS000714501) that inhibits LDH-A with an IC50 of approximately 20 μM with low efficacy that can be used as an anti-cancer therapeutic. Structure-activity relationship studies on this compound led to hydroxypryazole-based compounds and discovery that the hydroxypyrazole compound and related analogs demonstrated a strong metal-dependent activity. These efforts have ultimately led to derivatives of compounds of NCGC00345087 which have abrogated the Zn++ requirement for LDH-A inhibition and exhibit low nanomolar potency and favorable ADME properties. Agents that target enzymes involved in cancer cell metabolism are important because of their potential to preferentially target cancer tissues over normal tissues.
Commercial Applications
These compounds will be used as anti-cancer agents, both as a single agent therapy and in combination with existing agents.
Competitive Advantages
The compounds described represent some of the most potent and drug-like inhibitors of LDHA reported to date.

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