AR-42

• CAT Number: I011413
• CAS Number: 935881-37-1
• Molecular Formula: C18H20N2O3
• Molecular Weight: 312.36
• Purity: ≥95%
• Synonyms: N-hydroxy-4-[[(2S)-3-methyl-2-phenylbutanoyl]amino]benzamide
• InChI: InChI=1S/C18H20N2O3/c1-12(2)16(13-6-4-3-5-7-13)18(22)19-15-10-8-14(9-11-15)17(21)20-23/h3-12,16,23H,1-2H3,(H,19,22)(H,20,21)/t16-/m0/s1
• InChIKey: LAMIXXKAWNLXOC-INIZCTEOSA-N
• SMILES: CC(C)C(C1=CC=CC=C1)C(=O)NC2=CC=C(C=C2)C(=O)NO

AR-42 (HDAC-42; OSU-HDAC42) is a potent, orally bioavailable pan-HDAC inhibitor (IC50=16 nM). AR-42 induces growth inhibition, cell-cycle arrest, apoptosis, and activation of caspases-3/7. AR-42 promotes hyperacetylation of H3, H4, and alpha-tubulin, and up-regulation of p21. AR-42 shows cytotoxicity against various human cancer cell lines[1][2].
AR-42 (0.125-1 μM; 24 hours) inhibits cell proliferation in a dose-dependent manner, and the median IC50s for P815, C2, and BR cells are 0.65, 0.30, and 0.23 μM, respectively[3].
AR-42 (0.5 μM; 24 hours) induces cell-cycle arrest at G1 in the P815 cells and at G1/G2 in the C2 cells[3].
AR-42 (0.13-1 μM; 24 hours) causes a dose-dependent induction of apoptosis P815, C2, BR cells[3].
AR-42 (0.5-3 μM; 24 hours) induces hyperacetylation of histones H3 and H4 and α-tubulin[3].
AR-42 (10 mg/kg; tail vein injection; twice a week for three weeks) significantly inhibites tumor growth[4].

Reference

[1]. Lu YS, Chou CH, Tzen KY, Gao M, ChLu YS, et al. Radiosensitizing effect of a phenylbutyrate-derived histone deacetylase inhibitor in hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2012 Jun 1;83(2):e181-9.eng AL, Kulp SK, Cheng JC.Radiosensitizing effect of a phenylbutyrate-derived histone deacetylase inhibitor in hepatocellular carcinoma.Int J Radiat Oncol Biol Phys. 2012 Jun 1;83(2):e181-9. Epub 2012 Feb 28.
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[2]. Lu Q, et al. Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. J Med Chem. 2005 Aug 25;48(17):5530-5.
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[3]. Lin TY, et al. AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit. Blood. 2010 May 27;115(21):4217-25.
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[4]. Zhang M, et al. AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition. Oncotarget. 2016 Apr 19;7(16):22285-94.
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