HS-72

HS-72 is a highly selective, cell-permeable, allosteric small molecule inhibitor of inducible heat shock protein 70 (Hsp70i, also known as Hsp72 or HSPA1A/B). Discovered using a fluorescence-linked enzyme chemoproteomic strategy (FLECS), HS-72 binds to cysteine 306 (C306) in the ATPase domain of Hsp70i, reducing its affinity for ATP and altering its chaperone functions. Unlike other Hsp70 inhibitors, HS-72 selectively discriminates Hsp70i from the closely related, constitutively active homolog Hsc70. It has demonstrated preclinical efficacy in reducing tumor growth in HER2+ breast cancer models, inhibiting dengue virus (DENV) entry, correcting ATP7B-H1069Q mutant trafficking in Wilson's disease models, and improving graft function and cell viability in kidney transplant models following cold storage.

Other names

(S)-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1-(pyrazin-2-yl)piperidine-3-carboxamideHS72HS-72HS 72