KNK437 - CAS 218924-25-5
Catalog number: B0084-470906
Category: Inhibitor
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KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.
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Catalog Number Size Price Stock Quantity
B0084-470906 50 mg $278 In stock
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Solid powder
KNK-437; KNK 437.
3 years -20℃powder;6 months-80℃in solvent
Shelf Life:
2 years if stored properly
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1.HSP72 functionally inhibits the anti-neoplastic effects of HDAC inhibitors.
Fujii K;Suzuki N;Jimura N;Idogawa M;Kondo T;Iwatsuki K;Kanekura T J Dermatol Sci. 2018 Apr;90(1):82-89. doi: 10.1016/j.jdermsci.2018.01.002. Epub 2018 Jan 31.
BACKGROUND: ;The anticancer effects of histone deacetylase inhibitors (HDACi) vary between patients, and their molecular mechanisms remain poorly understood. Previously, we have identified heat shock 70 kDa protein 1A (HSPA1A, also known as HSP72) as the most overexpressed protein in valproic acid (VPA)-resistant cell lines. KNK437, an inhibitor of heat shock proteins, enhanced the cytotoxic effects of not only VPA but also vorinostat, another HDACi. However, the mechanisms underlying the role of HSP72 in resistance against HDACi remain largely unknown.;OBJECTIVE: ;The purpose of this study was to identify the mechanisms underlying the role of HSP72 in HDACi resistance.;METHODS: ;We established an HSP72-overexpressing Jurkat cell line and used it to assess the functional role of HSP72 following treatment with the HDACi vorinostat and VPA.;RESULTS: ;HDACi-induced apoptosis, assessed using annexin V assays, sub-G1 fraction analysis, and PARP cleavage, was significantly lower in HSP72-overexpressing cells than in control cells. The HDACi-induced upregulation in caspase-3, -8, and -9 activity, as well as the HDACi-induced reduction in mitochondrial membrane potential, were also suppressed following HSP72 overexpression.
2.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.
In this study, we compared the effect of KNK437 (N-formyl-3, 4-methylenedioxy-benzylidene-gamma-butyrolactam), a benzylidene lactam compound, on heat shock and chemical stressor-induced hsp30 gene expression in Xenopus laevis A6 kidney epithelial cells. Previously, KNK437 was shown to inhibit HSE-HSF1 binding activity and heat-induced hsp gene expression. In the present study, Northern and Western blot analysis revealed that pretreatment of A6 cells with KNK437 inhibited hsp30 mRNA and HSP30 and HSP70 protein accumulation induced by chemical stressors including sodium arsenite, cadmium chloride and herbimycin A. In A6 cells subjected to sodium arsenite, cadmium chloride, herbimycin A or a 33 degrees C heat shock treatment, immunocytochemistry and confocal microscopy revealed that HSP30 accumulated primarily in the cytoplasm. However, incubation of A6 cells at 35 degrees C resulted in enhanced HSP30 accumulation in the nucleus. Pre-treatment with 100 microM KNK437 completely inhibited HSP30 accumulation in A6 cells heat shocked at 33 or 35 degrees C as well as cells treated with 10 microM sodium arsenite, 100 microM cadmium chloride or 1 microg/mL herbimycin A. These results show that KNK437 is effective at inhibiting both heat shock- and chemical stress-induced hsp gene expression in amphibian cells.
3.Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin.
Guo F;Rocha K;Bali P;Pranpat M;Fiskus W;Boyapalle S;Kumaraswamy S;Balasis M;Greedy B;Armitage ES;Lawrence N;Bhalla K Cancer Res. 2005 Nov 15;65(22):10536-44.
17-Allylamino-demethoxy geldanamycin (17-AAG) inhibits the chaperone association of heat shock protein 90 (hsp90) with the heat shock factor-1 (HSF-1), which induces the mRNA and protein levels of hsp70. Increased hsp70 levels inhibit death receptor and mitochondria-initiated signaling for apoptosis. Here, we show that ectopic overexpression of hsp70 in human acute myelogenous leukemia HL-60 cells (HL-60/hsp70) and high endogenous hsp70 levels in Bcr-Abl-expressing cultured CML-BC K562 cells confers resistance to 17-AAG-induced apoptosis. In HL-60/hsp70 cells, hsp70 was bound to Bax, inhibited 17-AAG-mediated Bax conformation change and mitochondrial localization, thereby inhibiting the mitochondria-initiated events of apoptosis. Treatment with 17-AAG attenuated the levels of phospho-AKT, AKT, and c-Raf but increased hsp70 levels to a similar extent in the control HL-60/Neo and HL-60/hsp70 cells. Pretreatment with 17-AAG, which induced hsp70, inhibited 1-beta-D-arabinofuranosylcytosine or etoposide-induced apoptosis in HL-60 cells. Stable transfection of a small interfering RNA (siRNA) to hsp70 completely abrogated the endogenous levels of hsp70 and blocked 17-AAG-mediated hsp70 induction, resulting in sensitizing K562/siRNA-hsp70 cells to 17-AAG-induced apoptosis.
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CAS 218924-25-5 KNK437

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