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Aldehyde dehydrogenase 3 family member A1 (ALDH3A1)

In vitro studies suggest ALDH3A1 inhibitors could help sensitize cancers to cyclophosphamide or related compounds. ALDH3A1 is overexpressed on some cancer cells and can lead to drug resistance by detoxifying phosphamide-based therapeutics. Enzyme kinetic and crystallographic studies identified an inhibitor that bound the aldehyde-binding pocket of ALDH3A1 and had selectivity for ALDH3A1 over other closely related enzymes. In human lung adenocarcinoma or glioblastoma cells expressing ALDH3A1, compared with primary human lung fibroblasts that did not express the enzyme, the inhibitor increased chemosensitivity to the cyclophosphamide analog mafosfamide. Next steps include evaluating toxicology and pharmacology of ALDH3A1 inhibitors.
Cyclophosphamide is a generic chemotherapeutic.

SciBX 7(6); doi:10.1038/scibx.2014.164
Published online Feb. 13, 2014

Provisional patent application filed; available for licensing

Parajuli, B. et al. J. Med. Chem.; published online Jan. 4, 2014;
Contact: Thomas D. Hurley, Indiana University School of Medicine, Indianapolis, Ind.