KNK437 - CAS 218924-25-5
Catalog number: B0084-470906
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C13H11NO4
Molecular Weight:
245.23
COA:
Inquire
Targets:
HSP
Description:
KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.
Ordering Information
Catalog Number Size Price Stock Quantity
B0084-470906 50 mg $278 In stock
Bulk Inquiry
Purity:
98%
Appearance:
Solid powder
Synonyms:
KNK-437; KNK 437.
Solubility:
DMSO,15mg/mLwarmed(61.16mM);Water,<1mg/mL(<1mM);Ethanol,<1mg/mL(<1mM)
Storage:
3 years -20℃powder;6 months-80℃in solvent
MSDS:
Inquire
Shelf Life:
2 years if stored properly
Canonical SMILES:
O=CN1C(/C(CC1)=C\C2=CC=C(OCO3)C3=C2)=O
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.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related HSP Products


CAS 934343-74-5 Hsp990

Hsp990
(CAS: 934343-74-5)

Hsp980 is an orally bioavailable inhibitor of human heat-shock protein 90 (Hsp90) with potential antineoplastic activity.  Hsp980 binds to and inhibits the acti...

CAS 848695-25-0 BIIB021

BIIB021
(CAS: 848695-25-0)

BIIB021 is An orally active, purine-scaffold, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. BIIB021 that is ...

CAS 100872-83-1 ML346

ML346
(CAS: 100872-83-1)

ML346, a barbituric acid skeleton compound, is a novel activator of Hsp70 which could induce HSF-1-dependent chaperone expression and repair protein folding in ...

CAS 558640-51-0 VER-49009

VER-49009
(CAS: 558640-51-0)

VER-49009 a protein 90 (HSP90) inhibitor(IC50= 47 nM).

CAS 747413-08-7 VER-50589

VER-50589
(CAS: 747413-08-7)

VER-50589 is a potent Hsp90 inhibitor with IC50 of 21 nM for Hsp90β.

CAS 747412-49-3 Luminespib

Luminespib
(CAS: 747412-49-3)

Luminespib, also known as AUY-922 (or NVP-AUY922), is a derivative of 4,5-diarylisoxazole and a third-generation heat shock protein 90 (Hsp90) inhibitor with po...

CAS 847559-80-2 NVP-BEP800

NVP-BEP800
(CAS: 847559-80-2)

NVP-BEP800 is a novel, fully synthetic Hsp90β inhibitor with IC50 of 58 nM, exhibits >70-fold selectivity against Hsp90 family members Grp94 and Trap-1.

CAS 857402-23-4 Retaspimycin

Retaspimycin
(CAS: 857402-23-4)

Retaspimycin(IPI 504) is a small-molecule inhibitor of heat shock protein 90 (Hsp90) with antiproliferative and antineoplastic activities.Retaspimycin binds to ...

CAS 6809-52-5 Geranylgeranylacetone

Geranylgeranylacetone
(CAS: 6809-52-5)

Geranylgeranylacetone is commonly utilized to protect the gastric mucosa in peptic ulcer disease can induce expression of HSP70, HSPB8, and HSPB1.

CAS 857402-63-2 Retaspimycin Hydrochloride

Retaspimycin Hydrochloride
(CAS: 857402-63-2)

Retaspimycin HCl(IPI504 HCl) is the hydrochloride salt of a small-molecule inhibitor of Hsp90 with antineoplastic and antiproliferative activities. Retaspimycin...

CAS 218924-25-5 KNK437

KNK437
(CAS: 218924-25-5)

KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.

CAS 467214-21-7 Alvespimycin HCl

Alvespimycin HCl
(CAS: 467214-21-7)

Alvespimycin hydrochloride is the hydrochloride salt of alvespimycin, an analogue of the antineoplastic benzoquinone antibiotic geldanamycin. Alvespimycin binds...

CAS 912999-49-6 Onalespib

Onalespib
(CAS: 912999-49-6)

Onalespib, also known as AT13387, is a synthetic, orally bioavailable, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic a...

CAS 863774-58-7 Dimethylenastron

Dimethylenastron
(CAS: 863774-58-7)

Dimethylenastron is an inhibitor of mitotic motor kinesin Eg5 (IC50 = 200 nM).The inhibition of kinesin Eg5 by small molecules such as monastrol is currently ev...

CAS 1454619-14-7 PU-WS13

PU-WS13
(CAS: 1454619-14-7)

PU-WS13 is a cell-permeable inhibitor of Grp94 (EC50 = 220 nM).It shows selectivity for Grp94 over the related Hsps Trap-1, Hsp90α, and Hsp90β. PU-WS13 blocks t...

CAS 1134156-31-2 VER-155008

VER-155008
(CAS: 1134156-31-2)

VER-155008 is an adenosine-derived inhibitor of heat shock protein 70 (Hsp70; IC50 = 0.5 µM) that is selective over Hsp90.It targets the nucleotide-binding doma...

CAS 34157-83-0 Celastrol

Celastrol
(CAS: 34157-83-0)

Celastrol (tripterine) is a chemical compound isolated from the root extracts of Tripterygium wilfordii (Thunder god vine) and Celastrus regelii. Celastrol is a...

CAS 1268273-90-0 HSP70-IN-1

HSP70-IN-1
(CAS: 1268273-90-0)

HSP70-IN-1 is a heat shock protein (HSP) inhibitor that interferes with the formation of functional Hsp70-HOP-Hsp90 machinery, and it inhibits the growth of Kas...

CAS 101714-41-4 BIX

BIX
(CAS: 101714-41-4)

BIX is a BiP (Hsp70-5) ER chaperone inducer that induces BiP expression in vitro and in vivo. BIX protects against ER-stress induced cell death in neuronal and ...

CAS 1196723-93-9 HSF1A

HSF1A
(CAS: 1196723-93-9)

HSF1A is a cell-permeable human heat shock factor protein (HSP1) activator.

Chemical Structure

CAS 218924-25-5 KNK437

Quick Inquiry

Verification code

Featured Items