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Overview
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Background
Target: Hsp70IC50: N/ATRC 051384, belonging to substituted 2-propen-1-one class, is a potent inducer of heat shock protein 70 (HSP70) [1]. Induction of HSP70 is a natural response of stressed cells that protects neuronal cells from a variety of insults including acute ischemia. Therefore, induction of HSP70 provides a potential target for the treatment of stroke [1]. In vitro: Induction of HSP70 by TRC 051384 (6.25, and 12.5 μM) involved heat shock factor-1 (HSF1) activation in HeLa cells and led to increasing chaperone and anti-inflammatory activity [1]. Moreover, TRC 051384 (10-50 μM) dose-dependently induced HSPA1B overexpression in endothelial cells as well as leucocyte origin [2].In vivo: TRC 051384 (9 mg/kg, intra-peritoneal administration) treatment significantly decreased stroke-associated neuronal injury, disability, and increased survival in a rat model of transient ischemic stroke [1]. In addition, TRC 051384 (9 mg/kg, intra-peritoneal administration) delayed thrombus formation without increasing bleeding risk in WT mice [2].
1. Mohanan A, Deshpande S, Jamadarkhana PG, Kumar P, Gupta RC, Chauthaiwale V, et al. Delayed intervention in experimental stroke with TRC 051384--a small molecule HSP70 inducer. Neuropharmacology. 2011;60(6):991-9.
2. Allende M, Molina E, Guruceaga E, Tamayo I, Gonzalez-Porras JR, Gonzalez-Lopez TJ, et al. Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk. Cardiovasc Res. 2016;110(3):309-18.
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