Potent and Selective Inhibitors of Histone Deacetylase 6 (HDAC6): UIC-2016-026 & UIC-2017-075 & UIC-2021-077

Novel, selective HDAC6 inhibitors with enhanced potency, blood brain barrier penetrance, and selectivity. IC50: 2.3 nM; Papp(A−B): 4.58 x 10−6 cm/s; efflux ratio: 0.51. Upregulates α-tubulin acetylation with no effect on histone acetylation. Ameliorates cognitive deficits in Fragile X Syndrome, without altering cognition in wild-type mice. Combination treatment with anti-rejection drugs improves organ transplant retention when compared to anti-rejection drugs alone and preserved organ transplants in 100% of mice. Nelson Grihalde grihalde@otm.uic.edu 312-996-4129

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