867164-40-7

TRC051384, dose dependently induces HSP70B mRNA by several hundred folds in both HeLa and rat primary mixed neurons. Treatment with TRC051384 results in significant dose-dependent increase in HSF1 transcriptional activity and recovery of luciferase activity. TRC051384 results in 60% inhibition at 6.25 μM and 90% inhibition at 12.5 μM of LPS-induced TNF-α expression in differentiated THP-1 cell line.

Treatment with TRC051384 significantly reduces stroke associated neuronal injury (87% reduction in area of penumbra recruited to infarct, and 25% reduction in brain edema) and disability in a rat model of transient ischemic stroke even when administered 8 hours post onset of ischemia. Significant improvement in survival (50% by day2 and 67.3% by day 7) is observed with TRC051384 treatment initiated at 4 hours after ischemia onset. Induction of HSP70 by TRC051384 involves HSF1 activation and results in elevated chaperone and anti-inflammatory activity.