JG-2

JG-2 is a small molecule allosteric inhibitor of the 70 kDa heat shock protein (Hsp70) family. It was developed as a second-generation analog of the rhodacyanine dye MKT-077, featuring improved metabolic stability and potency. JG-2 binds to the nucleotide-binding domain (NBD) of Hsp70, specifically at an allosteric site that stabilizes the ADP-bound conformation. This stabilization inhibits the ATPase cycle of the chaperone, preventing it from effectively folding or maintaining the stability of its client proteins. In oncological contexts, JG-2 promotes the degradation of proteins like Akt and Raf-1, while in neurodegenerative research, it has been shown to reduce levels of the microtubule-associated protein tau. It is primarily used as a chemical probe and lead compound in preclinical studies for cancer and tauopathies.