image adapted from https://next.cancer.gov/discoveryResources/cbc.htm, Division of Cancer Treatment and Diagnosis, National Cancer Institute, part of the U.S. National Institutes of Health’
The American Chemical Society recently dedicated an issue of its ACS Medicinal Chemistry Letters journal to medicinal chemistry in Italy. As the editor’s introduction to this issue outlines, Italy has a strong track record in this field. This includes the successful discovery of drugs in IRBM’s laboratories, such as Raltegravir, Grazoprevir and Niraparib.
We were happy to contribute to this issue with an article that showcases some of the recent work undertaken at IRBM, focusing on non-hydroxamic class I HDAC inhibitors and HDAC3 selective inhibitors.
The use of first generation HDAC inhibitors has been hampered by their toxicity and suboptimal pharmacokinetic profile, which is in part associated with the zinc chelating group known as a hydroxamic warhead. The development of non-hydroxamic acid HDAC inhibitors showing isoform selectivity reduces unwanted toxicity and improves the pharmacokinetic profile. Moreover, it may also be a key step toward the use of HDAC inhibitors for non-oncological applications in therapeutic areas such as CNS, immunology and rare disease.
The article “Improved Selective Class I and Novel Selective HDAC3 Inhibitors: Beyond Hydroxamic Acids and Benzamides” can be found here.