ACY-1215

ACY-1215 is an inhibitor of the class IIb histone deacetylase (HDAC) HDAC6 (IC50 = 0.0047 µM). It is selective for HDAC6 over the class I HDACs HDAC1, -2, -3, and -8 (IC50s = 0.058, 0.048, 0.051, and 0.1 µM, respectively), class IIa HDACs HDAC4, -5, -7, and -9 (IC50s = 7, 5, 1.4 and >10 µM, respectively), class III HDACs sirtuin 1 (SIRT1) and SIRT2 (IC50s = >10 µM for both), and the class IV HDAC HDAC11 (IC50 = >10 µM). ACY-1215 (0.5-2.5 µM) induces accumulation of acetylated alpha-tubulin in OCI-LY10 diffuse large B cell lymphoma (DLBCL) cells and induces cytotoxicity in several multiple myeloma cell lines (IC50s = 2-8 µM). It decreases tumor volume and increases survival in an OCI-LY10 mouse xenograft model when administered at a dose of 50 mg/kg in combination with the 20S proteasome inhibitor bortezomib (Cay-10008822). ACY-1215 also decreases liver and kidney cyst area and liver fibrosis in PCK rats in a model of polycystic liver disease.Formal Name: 2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-5-pyrimidinecarboxamide. CAS Number: 1316214-52-4. Synonyms: ACY-63, Ricolinostat, Rocilinostat. Molecular Formula: C24H27N5O3. Formula Weight: 433.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 5 mg/ml, DMSO: 5 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml. lambdamax: 289 nm. SMILES: O=C(NCCCCCCC(NO)=O)C(C=N1)=CN=C1N(C2=CC=CC=C2)C3=CC=CC=C3. 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/h3-8,11-14,17-18,32H,1-2,9-10,15-16H2,(H,25,31)(H,28,30). InChi Key: QGZYDVAGYRLSKP-UHFFFAOYSA-N.