Definition

An orally bioavailable, synthetic flexible heteroarotinoid (Flex-Het), with antineoplastic activity. Upon oral administration, Flex-Het sulfur heteroarotinoid A2 (SHetA2) binds to the three related heat shock protein A (HSPA) chaperone proteins HSPA5 (78-kDa glucose-regulated protein; Grp78; BiP), HSPA8 (Hsc70) and HSPA9 (mortalin), and disrupts their binding to client proteins. This may induce G1 cell cycle arrest and apoptosis, and inhibit tumor cell growth, migration and invasion. Grp78, hsc70, and mortalin play important roles in ensuring the proper folding, function, and cellular localization of their client proteins, which are important for cell survival; they are mutated in certain cancer types.