1,6-Heptadiene-3,5-dione, 4-(cyclobutylmethyl)-1,7-bis(3,4-dimethoxyphenyl)-, (1E,6E)-

Rosolutamide (ASC-JM17), a curcumin analog, is an orally active, potent Nrf1 and Nrf2 activator. Rosolutamide activates Nrf1, Nrf2 and heat shock factor 1 (Hsf1), thereby activating the expression of proteasome subunits, antioxidant enzymes and molecular chaperones. Rosolutamide degrades the polyglutamine (polyQ) androgen receptor (AR) via the ubiquitin-proteasome pathway and improves motor function in mouse models of spinal and bulbar muscular atrophy (SBMA). Rosolutamide improves mitochondrial function and promotes autophagy, decreases mutant protein aggregates, and attenuates intracellular/mitochondrial reactive oxygen species (ROS) levels[1][2].

HSF1

[1] Laura C Bott, et al. A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy. Hum Mol Genet. 2016 May 15;25(10):1979-1989. DOI:10.1093/hmg/ddw073
[2] Yu-Ling Wu, et al. In Vitro Efficacy and Molecular Mechanism of Curcumin Analog in Pathological Regulation of Spinocerebellar Ataxia Type 3. Antioxidants (Basel). 2022 Jul 18;11(7):1389. DOI:10.3390/antiox11071389