Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 55, Issue 22, Pages 9891-9899Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm301098e
Keywords
-
Categories
Funding
- NIH [CA134807]
- International Rett Syndrome Foundation (IRSF)
Ask authors/readers for more resources
The incidence of malignant melanoma has dramatically increased in recent years thus requiring the need for improved therapeutic strategies. In our efforts to design selective histone deactylase inhibitors (HDACI), we discovered that the aryl urea 1 is a modestly potent yet nonselective inhibitor. Structure-activity relationship studies revealed that adding substituents to the nitrogen atom of the urea so as to generate compounds bearing a branched linker group results in increased potency and selectivity for HDAC6. Compound 5g shows low nanomolar inhibitory potency against HDAC6 and a selectivity of similar to 600-fold relative to the inhibition of HDACI. These HDACIs were evaluated for their ability to inhibit the growth of B16 melanoma cells with the most potent and selective HDAC6I being found to decrease tumor cell growth. To the best of our knowledge, this work constitutes the first report of HDAC6-selective inhibitors that possess antiproliferative effects against melanoma cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available