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| Product Name: | KNK437 | | Synonyms: | N-FORMYL-3,4-METHYLENEDIOXY-BENZYLIDINE-GAMMA-BUTYROLACTAM;3,4-METHYLENEDIOXY-BENZYLIDINE-GAMMA-BUTYROLACTAM;KNK423;KNK437;HEAT SHOCK PROTEIN INHIBITOR I;HEAT SHOCK PROTEIN INHIBITOR II;3-(1,3-Benzodioxol-5-ylmethylene)-2-oxo-1-pyrrolidinecarboxaldehyde;Heat Shock Protein Inhibitor I - CAS 218924-25-5 - Calbiochem | | CAS: | 218924-25-5 | | MF: | C13H11NO4 | | MW: | 245.23 | | EINECS: | | | Product Categories: | API;Inhibitors | | Mol File: | Mol File |  |
| | KNK437 Chemical Properties |
| 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. |
| | KNK437 Usage And Synthesis |
| 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 |
| | KNK437 Preparation Products And Raw materials |
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