| Identification | Back Directory | [Name]
3,4-METHYLENEDIOXY-BENZYLIDINE-GAMMA-BUTYROLACTAM | [CAS]
218924-25-5 | [Synonyms]
KNK423
KNK437
CS-1681
KNK-437;KNK 437
HEAT SHOCK PROTEIN INHIBITOR I
HEAT SHOCK PROTEIN INHIBITOR II
3,4-METHYLENEDIOXY-BENZYLIDINE-GAMMA-BUTYROLACTAM
N-Formyl-3,4-methylenedioxy-benzylidene-g-butyrolactam
N-FORMYL-3,4-METHYLENEDIOXY-BENZYLIDINE-GAMMA-BUTYROLACTAM
Heat Shock Protein Inhibitor I - CAS 218924-25-5 - Calbiochem
3-(1,3-Benzodioxol-5-ylmethylene)-2-oxo-1-pyrrolidinecarboxaldehyde
3-[(E)-1,3-Benzodioxol-5-ylmethylene]-2-oxopyrrolidine-1-carbaldehyde
1-Pyrrolidinecarboxaldehyde, 3-(1,3-benzodioxol-5-ylmethylene)-2-oxo- | [Molecular Formula]
C13H11NO4 | [MDL Number]
MFCD03453551 | [MOL File]
218924-25-5.mol | [Molecular Weight]
245.23 |
| Chemical Properties | Back Directory | [Boiling point ]
412.4±55.0 °C(Predicted) | [density ]
1.515±0.06 g/cm3(Predicted) | [storage temp. ]
room temp | [solubility ]
DMSO: soluble5mg/mL, clear (warmed) | [form ]
White to light yellow powder | [pka]
-1.70±0.20(Predicted) | [color ]
white to beige | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [InChI]
1S/C13H11NO4/c15-7-14-4-3-10(13(14)16)5-9-1-2-11-12(6-9)18-8-17-11/h1-2,5-7H,3-4,8H2 | [InChIKey]
LZGGUFLRKIMBDQ-UHFFFAOYSA-N | [SMILES]
N1(CCC(=Cc2cc3c(cc2)OCO3)C1=O)C=O |
| Hazard Information | Back Directory | [Description]
KNK437 (218924-25-5) Inhibits constitutive and inducible HSP70 expression in non-stressed1 and heat-stressed2 cancer cells. Blocks the geldanamycin-induced induction of HSP70 and inhibition of TGF? signaling.3 Inhibits leukocyte integrin α4?7-mediated adhesion of T cells to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) suggesting that HSP70 is essential for ?7 integrin signalling.4 Suppresses morphine analgesic tolerance in a rodent model (100 mg/Kg).5 | [Uses]
KNK437 has been used:
- as a heat shock factor 1 (HSF1) inhibitor to study its effects on the inhibition of viability and apoptosis activation in chemoresistant mice cells
- as an HSF1 inhibitor to study its effects on viability and apoptosis of colorectal cancer cells
- as a heat shock protein 70 (HSP70) inhibitor to study its effects on glutamine-induced HSP70 and inflammatory mediator release
| [Biological Activity]
KNK437 is a pan-HSP inhibitor that inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40. | [Biochem/physiol Actions]
KNK437 inhibits the accumulation of heat shock proteins (including hsp -27, -40, -70, -72 and -105). KNK437 inhibits thermotolerance in cells with greater potency than quercetin. | [in vitro]
In COLO320DM (human colon cancer) cells, KNK437 dose-dependently inhibits acquisition of thermotolerance and the activity of various HSPs, including Hsp105, HSP70 and HSP40. In PC-3 cells, KNK437 and quercetin dose-dependently inhibited thermotolerance. In PC-3 and LNCaP cells, KNK437 reduced heat-induced accumulation of HSP70 mRNA and protein. | [in vivo]
KNK437 (200 mg/kg, intraperitoneal injection) showed no antitumor effect and did not increase the thermosensitivity of non-tolerant tumors. The same dose of KNK437 can synergistically improve the antitumor efficacy of graded heat treatment. | [References]
Shiota et al. (2010), Heat shock cognate protein 70 is essential for Akt signaling in endothelial function; Thromb. Vasc. Biol., 30 491
Yokota et al. (2000), Benzylidene lactam compound, KNK437, a novel inhibitor of acquisition of thermotolerance and heat shock protein induction in human colon carcinoma cells; Cancer Res., 60 2942
Yun et al. (2010), Geldanamycin inhibits TGF-beta signaling through induction of Hsp70; Biochem. Biophys., 495 8
Chan et al. (2015), Leukocyte integrin α4?7 associates with heat shock protein 70; Cell. Biochem., 409 263
Qin et al. (2020), Effect of heat chock protein 70 modulators on the development of morphine analgesic tolerance in rats; Pharmacol., 31 179 |
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