LMK235
Potent, selective inhibitor of HDAC4/5 / Potent and selective inhibitor of HDAC4 (IC50 = 11.9 nM) and HDAC5 (IC50 = 4.2 nM).1 Cytotoxic against human ovarian cancer cell lines A2780 and A2780 CisR (IC50’s = 0.49 µM and 0.32 µM respectively). It displayed synergistic effects with cisplatin and restored sensitivity in platinum-resistant cell lines.1,2 LMK235 induced apoptosis in pancreatic neuroendocrine tumor cell lines BON-1 and QGP-13 and in multiple myeloma cells4. It also induced autophagy and cell death via SCNN1A downregulation in glioblastoma cells.5 LMK235 reduced hypertension in mouse and rat models via inhibition of vascular constriction and vessel hypertrophy.6 LMK235 significantly increased neurite outgrowth via increased BMP-Smad-dependent transcription in SH-SY5Y cells and exerted neuroprotective effects against neurodegeneration induced by MPP+ suggesting possible therapeutic potential in treating Parkinson’s disease.7
Biochemicals & reagents
1418033-25-6
1 Marek et al. (2013), Histone Deacetylase (HDAC) Inhibitors with a Novel Connecting Unit Linker Region Reveal a Selectivity Profile for HDAC4 and HDAC 5 with Improved Activity against Chemoresistant Cancer Cells; J. Med. Chem. 56 427 2 Moita et al. (2020), Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors; Int. J. Mol. Sci. 21 8300 3 Wanek et al. (2018), Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells; Int. J. Mol. Sci. 19 3128 4 Li et al. (2019), Histone deacetylase inhibitor LMK-235-mediated HO-1 expression induces apoptosis I multiple myeloma cells via JNK/AP-1 signaling pathway; Life Sci. 223 146 5 Chang et al. (2022), A Selective Histone deacetylase inhibitor LMK235 Induces Autophagy and Cell Death via SCNN1A Downregulation in Glioblastoma Cells; Cancers (Basel) 14 4537 6 Choi et al. (2019), Histone deacetylase inhibitor LMK235 attenuates vascular constriction and aortic remodeling in hypertension; J. Cell Mol. Med. 23 2801 7 Mazzocchi et al. (2021), LMK235, a small molecules inhibitor of HDAC4/5, protects dopaminergic neurons against neurotoxin- and α-synuclein-induced degeneration in cellular models of Parkinson’s disease; Mol. Cell Neurosci. 115 103642
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TARGET: Protein deacetylase -- PATHWAY: Chromatin; Posttranslational modification; Senescence -- RESEARCH AREA: Epigenetics; Neuroscience; Oxidative stress -- DISEASE AREA: Cancer; NeurodegenerationParasites; Hypertension