Uses
N-[2-(4-Morpholinyl)ethyl]-N''-[4-[3-[6-(4-morpholinyl)-2-pyridinyl]-1-oxo-2-propen-1-yl]phenyl]urea is a key reactant in the synthesis of TRC051384, which is a small molecule HSP70 inducer.
Biological Activity
trc 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].
References
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.
