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Overview
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Background
KNK437 is a benzylidene lactam compound that inhibits stress-induced HSPs (heat shock proteins) synthesis.
HSPs (heat shock proteins) are chaperones that their expressions are increased under various cellular stresses including temperature rise. It plays a vital role in regulating protein folding and associated with cancer and cardiovascular diseases.
KNK437 inhibits the acquisition of thermotolerance and the induction of various HSPs in human colon carcinoma cells (COLO 320DM) in a dose-dependent manner. KNK437 also blocks the acquisition of thermotolerance that developed by sodium arsenite. [1]
KNK437 exerts low toxicity in vivo. In C3H/He mice transplanted with SCC VII cells, the concentration of KNK437 in the tumors gradually increases and reaches a peak 6 hours after i.p. injection. Hsp72 were synthesized 8 h after hyperthermia at 44 oC for 10 minutes, and their synthesis is inhibited by administration of KNK437 6 hours before hyperthermia. [2]1. Yokota S, Kitahara M, Nagata K. Benzylidene lactam compound, KNK437, a novelinhibitor of acquisition of thermotolerance and heat shock protein induction inhuman colon carcinoma cells. Cancer Res. 2000 Jun 1;60(11):2942-8.
2. Koishi M, Yokota S, Mae T et al. The effects of KNK437, a novel inhibitor of heat shock proteinsynthesis, on the acquisition of thermotolerance in a murine transplantable tumor in vivo. Clin Cancer Res. 2001 Jan;7(1):215-9.
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