General description

A cell-permeable S-isobutyryl prodrug that is processed intracellularly to form the potent HDAC inhibitor NCH-31 (IC50 = 48 and 170 nM, respectively, using partially purified HDAC1 or HeLa nuclear extract) that is predicted to exhibit a similar HADC binding mode as that of SAHA with its sulfhydryl replacing SAHA′s hydroxamate as the active-site zinc-targeting group. NCH-51 is shown to exhibit comparable antiproliferative (mean IC₅₀ = 3.8 µM vs. 3.7 µM for SAHA; 48 h treatment) and apoptotic activity as SAHA against various cancer cell lines, but not PBMCs from 4 healthy individuals (IC₅₀ >30 µM with either drug), and the antioxidant N-Acetyl-L-Cysteine (NAC; Cat. No. 106425) at 2 mM is reported to abolish the cell-growth inhibition caused by either 3 µM NCH-51 or SAHA in the Multiple Myeloma U266 cultures. Half-life in human plasma at 37 °C = 24 h.

A cell-permeable S-isobutyryl prodrug that is processed intracellularly to form the potent HDAC inhibitor NCH-31 (IC50 = 48 and 170 nM, respectively, using partially purified HDAC1 or HeLa nuclear extract) that is predicted to exhibit a similar HADC binding mode as that of SAHA with its sulfhydryl replacing SAHA′s hydroxamate as the active-site zinc-targeting group. NCH-51 is shown to exhibit comparable antiproliferative (mean IC₅₀ = 3.8 µM vs. 3.7 µM for SAHA; 48 h treatment) and apoptotic activity as SAHA against various cancer cell lines, but not PBMCs from 4 healthy individuals (IC₅₀ >30 µM with either drug), and the antioxidant N-Acetyl-L-Cysteine (NAC; Cat. No. 106425) at 2 mM is reported to abolish the cell-growth inhibition caused by either 3 µM NCH-51 or SAHA in the Multiple Myeloma U266 cultures. Half-life in human plasma at 37 °C = 24 h.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

#31: Thiol - 7-Mercaptoheptanoic acid (4-phenyl-2-thiazolyl)amide

Sanda, T., et al. 2007. Leukemia21, 2344.Suzuki, T., et al. 2007. Bioorg. Med. Chem. Lett.17, 1558.Suzuki, T., et al. 2005. J. Med. Chem.48, 1019.

Packaging

2 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Regulatory Review (Z)