Synonym: ACY-1215; ACY1215; ACY 1215; Rocilinostat

IUPAC/Chemical Name: 2-(diphenylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide

InChi Key: QGZYDVAGYRLSKP-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H27N5O3/c30-22(28-32)15-9-1-2-10-16-25-23(31)19-17-26-24(27-18-19)29(20-11-5-3-6-12-20)21-13-7-4-8-14-21/h4-8,11-14,17-18,32H,1-2,9-10,15-16H2,(H,25,31)(H,28,30)

SMILES Code: O=C(C1=CN=C(N(C2=CC=CC=C2)C3=CC=CC=C3)N=C1)NCCCCCCC(NO)=O

Technical Data

Additional Information

ACY-1215 selectively inhibits the intracellular enzyme HDAC6, leading to inactivation of the “aggresome” pathway for degradation of damaged proteins. The resultant accumulation of excess waste protein in malignant cells triggers programmed cell death, called “apoptosis,” with little or no effect on normal cells. Currently available HDAC drugs non-selectively target multiple HDAC enzymes including those of Class I, resulting in dysregulated expression of numerous genes in normal cells as well as cancer cells. Side effects commonly associated with non-selective HDAC drugs include gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage, and profound fatigue as well as potential for severe cardiac complications. Selective inhibition of HDAC6 is expected to reduce or eliminate these often-severe side effects associated with non-selective HDAC inhibition, and may enable the development of optimized treatment regimens including maximally effective combination drug therapies. (source: http://www.acetylon.com/).   
 
 ACY-1215 demonstrated potent and selective inhibitory activity against HDAC6, with an enzymatic IC50 value of 5nM. ACY-1215 is 12-, 10-, and 11-fold less active against HDAC1, HDAC2, and HDAC3 (class I HDACs), respectively. ACY-1215 has minimal activity  (IC50 1 M) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and has slight activity against HDAC8 (IC50 0.1 M).
 ACY-1215 demonstrated potent and selective inhibitory activity against HDAC6, with an enzymatic IC50 value of 5nM. ACY-1215 is 12-, 10-, and 11-fold less active against HDAC1, HDAC2, and HDAC3 (class I HDACs), respectively. ACY-1215 has minimal activity  (IC50 1 M) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and has slight activity against HDAC8 (IC50 0.1 M).
 
 

References

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