AR-42

Intact male NCr athymic nude mice inoculated s.c. with PC-3 cells

(S)-N-hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide

Dissolved in DMSO, final concentrations ca.2.5 uM

ca.50 mg/kg/day

Formulated in methylcellulose/Tween 80

AR-42 treatment induces histone hyperacetylation and p21WAF/CIP1 overexpression, and inhibits the growth of DU-145 cells with IC50 of 0.11 uM. [1] HDAC42 is potent in suppressing the proliferation of U87MG and PC-3 cells, in part, because of its ability to down-regulate Akt signaling. [2] AR-42 inhibits the growth of PC-3 and LNCaP cells with IC50 of 0.48 uM and 0.3 uM, respectively. Compared to SAHA, AR-42 exhibits distinctly superior apoptogenic potency, and causes markedly greater decreases in phospho-Akt, Bcl-xL, and survivin in PC-3 cells. [3] AR-42 treatment induces growth inhibition, cell- cycle arrest, apoptosis, and activation of caspases-3/7 in malignant mast cell lines. AR-42 treatment induces down-regulation of Kit via inhibition of Kit transcription, disassociation between Kit and heat shock protein 90 (HSP90), and up-regulation of HSP70. AR-42 treatment down-regulates the expression of p-Akt, total Akt, phosphorylated STAT3/5 (pSTAT3/5), and total STAT3/5. [6] AR-42 potently inhibits the growth of JeKo-1, Raji, and 697 cells with IC50 of <0.61 uM. AR-42 also sensitizes CLL cells to TNF-Related Apoptosis Inducing Ligand (TRAIL), potentially through reduction of c-FLIP. [7] AR-42 treatment also induces autophagy through downregulation of Akt/mTOR signaling and inducing ER stress in hepatocellular carcinoma (HCC) cells. [8]

96 hours

Cells are exposed to varous concentrations of AR-42 for 96 hours. The medium is removed and replaced by 150 L of 0.5 mg/mL of MTT in RPMI 1640 medium, and the cells are incubated in the CO2 incubator at 37 C for 2 hours. Supernatants are removed from the wells, and the reduced MTT dye is solubilized with 200 L/well of DMSO. Absorbance is determined on a plate reader at 570 nm.

AR-42 (HDAC-42) Chemical Structure

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO