848354-66-5 Usage
Uses
NCH 51 is a Histone deacetylase inhibitor.
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.
Biological Activity
Histone deacetylase (HDAC) inhibitor. Inhibits growth of various cancer cells in vitro (EC 50 = 1.1-9.1 μ M).
Biochem/physiol Actions
HDAC inhibitor; more potent than the majority of HDAC inhibitors except for SAHA (gold standard).
references
[1]. suzuki t, hisakawa s, itoh y, et al. identification of a potent and stable antiproliferative agent by the prodrug formation of a thiolate histone deacetylase inhibitor. bioorg med chem lett, 2007, 17(6): 1558-1561. [2]. suzuki t, nagano y, kouketsu a, et al. novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of saha-based non-hydroxamates. j med chem, 2005, 48(4): 1019-1032.[3]. sanda t, okamoto t, uchida y, et al. proteome analyses of the growth inhibitory effects of nch-51, a novel histone deacetylase inhibitor, on lymphoid malignant cells. leukemia, 2007, 21(11): 2344-2353. [4]. victoriano af, imai k, togami h, et al. novel histone deacetylase inhibitor nch-51 activates latent hiv-1 gene expression. febs lett, 2011, 585(7): 1103-1111.
Check Digit Verification of cas no
The CAS Registry Mumber 848354-66-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,4,8,3,5 and 4 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 848354-66:
(8*8)+(7*4)+(6*8)+(5*3)+(4*5)+(3*4)+(2*6)+(1*6)=205
205 % 10 = 5
So 848354-66-5 is a valid CAS Registry Number.
InChI:InChI=1/C20H26N2O2S2/c1-15(2)19(24)25-13-9-4-3-8-12-18(23)22-20-21-17(14-26-20)16-10-6-5-7-11-16/h5-7,10-11,14-15H,3-4,8-9,12-13H2,1-2H3,(H,21,22,23)
848354-66-5Relevant articles and documents
Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates
Suzuki, Takayoshi,Nagano, Yuki,Kouketsu, Akiyasu,Matsuura, Azusa,Maruyama, Sakiko,Kurotaki, Mineko,Nakagawa, Hidehiko,Miyata, Naoki
, p. 1019 - 1032 (2007/10/03)
To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong activity, and its potency was comparable to that of SAHA. The cancer cell growth inhibitory activity was verified to be the result of histone hyperacetylation and subsequent induction of p21WAF1/CIP1 by Western blot analysis. Kinetical enzyme assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis within the cell interacts with the zinc ion in the active site of HDACs.
