KNK437

• CAT Number: I002673
• CAS Number: 218924-25-5
• Molecular Formula: C13H11NO4
• Molecular Weight: 245.2
• Purity: ≥95%
• Synonyms: (E)-2-(benzo[d][1,3]dioxol-5-ylmethylene)-5-oxopyrrolidine-1-carbaldehyde
• Target: HSP
• Solubility: DMSO≥ 34 mg/mL
• Storage: Store at -20°C
• IC50: 17 umol/L
• InChIKey: LZGGUFLRKIMBDQ-BJMVGYQFSA-N

KNK437(CAT: I002673) is a compound that has been shown to inhibit the acquisition of thermotolerance and the induction of heat shock proteins (HSPs). It has been studied in the context of cancer cells, specifically COLO 320DM cells, which are human colon carcinoma cells. KNK437 demonstrated a dose-dependent inhibition of thermotolerance and the induction of various HSPs, including HSP105, HSP70, and HSP40, in these cells. The ability of KNK437 to modulate heat shock response pathways may have implications in cancer therapy and the understanding of cellular stress responses.

Reference

1:An in vitro model to consider the effect of 2 mM glutamine and KNK437 on endotoxin-stimulated release of heat shock protein 70 and inflammatory mediators. Marino LV, Pathan N, Meyer RW, Wright VJ, Habibi P.Nutrition. 2016 Mar;32(3):375-83. doi: 10.1016/j.nut.2015.09.007. Epub 2015 Sep 30. PMID: 26706024 2:KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1α survival pathways. Oommen D, Prise KM.Biochem Biophys Res Commun. 2012 May 11;421(3):538-43. doi: 10.1016/j.bbrc.2012.04.040. Epub 2012 Apr 13. PMID: 22521642 3:KNK437, a benzylidene lactam compound, sensitises prostate cancer cells to the apoptotic effect of hyperthermia. Sahin E, Sahin M, Sanlioğlu AD, Gümüslü S.Int J Hyperthermia. 2011;27(1):63-73. doi: 10.3109/02656736.2010.528139. Epub 2011 Jan 4. PMID: 21204621 4:KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine. Taba K, Kuramitsu Y, Ryozawa S, Yoshida K, Tanaka T, Mori-Iwamoto S, Maehara S, Maehara Y, Sakaida I, Nakamura K.Chemotherapy. 2011;57(1):12-6. doi: 10.1159/000321019. Epub 2010 Dec 3. PMID: 21124027 5:N-Formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolaetam, KNK437 induces caspase-3 activation through inhibition of mTORC1 activity in Cos-1 cells. Inoue H, Uyama T, Hayashi J, Watanabe A, Kobayashi K, Tadokoro T, Yamamoto Y.Biochem Biophys Res Commun. 2010 Apr 23;395(1):56-60. doi: 10.1016/j.bbrc.2010.03.134. Epub 2010 Mar 27. PMID: 20350529 6:Heat shock protein inhibitors, 17-DMAG and KNK437, enhance arsenic trioxide-induced mitotic apoptosis. Wu YC, Yen WY, Lee TC, Yih LH.Toxicol Appl Pharmacol. 2009 Apr 15;236(2):231-8. doi: 10.1016/j.taap.2009.02.003. Epub 2009 Feb 12. PMID: 19371599 7:Comparison of the effect of heat shock factor inhibitor, KNK437, on heat shock- and chemical stress-induced hsp30 gene expression in Xenopus laevis A6 cells. Voyer J, Heikkila JJ.Comp Biochem Physiol A Mol Integr Physiol. 2008 Oct;151(2):253-61. doi: 10.1016/j.cbpa.2008.07.004. Epub 2008 Jul 10. PMID: 18675372 8:Examination of KNK437- and quercetin-mediated inhibition of heat shock-induced heat shock protein gene expression in Xenopus laevis cultured cells. Manwell LA, Heikkila JJ.Comp Biochem Physiol A Mol Integr Physiol. 2007 Nov;148(3):521-30. Epub 2007 Jul 5. PMID: 17681842 9:Effects of KNK437 on heat-induced methylation of histone H3 in human oral squamous cell carcinoma cells. Matsuda K, Nakagawa SY, Nakano T, Asaumi J, Jagetia GC, Kawasaki S.Int J Hyperthermia. 2006 Dec;22(8):729-35. PMID: 17391001 10:The heat shock protein inhibitor KNK437 induces neurite outgrowth in PC12 cells. Koike T, Uno S, Ishizawa M, Takahashi H, Ikeda K, Yokota S, Makishima M.Neurosci Lett. 2006 Dec 27;410(3):212-7. Epub 2006 Oct 18. PMID: 17055158