NKL 22 (MDK-4154)

• CAT Number: I003959
• CAS Number: 537034-15-4
• Molecular Formula: C₁₉H₂₃N₃O₂
• Molecular Weight: 325.4
• Purity: ≥95%
• Target: HDAC inhibitor IV
• Solubility: 29 mg/mL
• Storage: -20°C
• InChI: 1S/C19H23N3O2/c20-16-11-7-8-12-17(16)22-19(24)14-6-2-5-13-18(23)21-15-9-3-1-4-10-15/h1,3-4,7-12H,2,5-6,13-14,20H2,(H,21,23)(H,22,24)
• InChIKey: ZAIULUYKQLVQFH-UHFFFAOYSA-N
• SMILES: C1=CC=C(C=C1)NC(=O)CCCCCC(=O)NC2=CC=CC=C2N

NKL 22 (MDK-4154)(CAT: I003959) is a histone deacetylase (HDAC) inhibitor. It exhibits an IC50 value of 78 μM, indicating its potency as an HDAC inhibitor. NKL 22 has been found to increase frataxin protein concentrations, which is beneficial in the context of Friedrich’s ataxia (FRDA), a neurodegenerative disorder associated with low frataxin levels. Additionally, NKL 22 and other HDAC inhibitors have been shown to increase FXN mRNA levels in FRDA lymphocytes, suggesting a direct effect on the FXN gene. These findings highlight the potential of NKL 22 as a therapeutic agent for FRDA and suggest that HDAC inhibitors may directly impact frataxin expression.

Reference

1:J Cell Biochem. 2016 Aug;117(8):1855-68. doi: 10.1002/jcb.25485. Epub 2016 Feb 2. TSC-22 Promotes Interleukin-2-Deprivation Induced Apoptosis in T-Lymphocytes.Pépin A,Espinasse MA,Latré de Laté P,Szely N,Pallardy M,Biola-Vidamment A, PMID: 26752201 DOI: 10.1002/jcb.25485 Abstract: Originally described as a TGF-β-inducible gene, tsc-22 (Transforming growth factor-beta Stimulated Clone 22) encodes a transcriptional regulator affecting biological processes such as cell growth, differentiation, or apoptosis. Along with GILZ (Glucocorticoid-Induced Leucine Zipper), TSC-22 belongs to the evolutionary conserved TSC-22 Domain family. We previously showed that, in T-lymphocytes, GILZ expression was induced upon IL-2 withdrawal, delaying apoptosis through down-regulation of the pro-apoptotic protein BIM expression. The aim of this work was then to elucidate the respective roles of GILZ and TSC-22 upon IL-2 deprivation-induced apoptosis. We report here that these two highly homologous genes are concomitantly expressed in most human tissues and in primary T-lymphocytes and that expression of TSC-22 promotes T-lymphocytes apoptosis by inhibiting GILZ functions. Indeed, we demonstrated that TSC-22 expression in the murine lymphoid CTLL-2 cell line promoted IL-2 deprivation-induced apoptosis. BIM expression and caspases-9 and -3 activities were markedly increased in TSC-22 expressing clones compared to control clones. Analysis of GILZ expression revealed that TSC-22 prevented the induction of the GILZ protein upon IL-2 deprivation, by inhibiting gilz mRNA transcription. These results suggested that TSC-22 could counteract the protective effect of GILZ on IL-2-deprivation-induced apoptosis. Moreover, TSC-22-induced inhibition of GILZ expression was also found in CTLL-2 cells treated with glucocorticoids or TGF-β. In the human NKL cell line deprived of IL-2, TSC-22 showed the same effect and thus may represent a potent repressor of GILZ expression in IL-2-dependent cells, independently of the cell type, or the stimulus, leading to an increase of IL-2-deprived T-cells apoptosis. J. Cell. Biochem. 117: 1855-1868, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.