| Description | AR-42(HDAC-42) is a HDAC inhibitor with IC50 30 nM.IC50 Value: 30 nMTarget: HDACin vivo: HDAC42 is potent in suppressing the proliferation of U87MG and PC-3 cells, in part, because of its ability to down-regulate Akt signaling. AR-42 inhibits the growth of PC-3 and LNCaP cells with IC50 of 0.48 μM and 0.3 μM, 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. 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. in vitro: In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, administration of AR-42 not only decreases the severity of prostatic intraepithelial neoplasia (PIN) and completely prevents its progression to poorly differentiated carcinoma, but also shifts tumorigenesis to a more differentiated phenotype, suppressing absolute and relative urogenital tract weights by 86% and 85%, respectively. AR-42 significantly reduces leukocyte counts, and prolongs survival in three separate mouse models of B-cell malignancy without evidence of toxicity. |
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| References | [1]. Lu YS, Chou CH, Tzen KY, Gao M, Cheng 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. [2]. Zimmerman B, Sargeant A, Landes K, Fernandez SA, Chen CS, Lairmore MD.Efficacy of novel histone deacetylase inhibitor, AR42, in a mouse model of, human T-lymphotropic virus type 1 adult T cell lymphoma.Leuk Res. 2011 Nov;35(11):1491-7. Epub 2011 Jul 29. [3]. Zhang S, Suvannasankha A, Crean CD, White VL, Chen CS, Farag SS.The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and induces apoptosis and cell cycle arrest in multiple myeloma cells.Int J Cancer. 2011 Jul 1;129(1):204-13. [4]. 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. [5]. Shuhong Zhang et al. The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and induces apoptosis and cell cycle arrest in multiple myeloma cells International Journal of Cancer Volume 129, Issue 1, pages 204-213, 1 July 2011 |
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