sb 02024

Fmoc-9-aminononanoic acid is an alkane chian with terminal Fmoc-protected amine and carboxylic acid groups. The compound can be used as a PROTAC linker in the synthesis of PROTACs and and other conjugation applications. The Fmoc group can be deprotected under basic condition to obtain the free amine which can be used for further conjugations. The terminal carboxylic acid can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond.

SB02024 is a VPS34 inhibitor. SB02024 activates cGAS-STING signaling and sensitizes tumors to STING agonist. SB02024 blocked autophagy in vitro and reduced xenograft growth of two breast cancer cell lines, MDA-MB-231 and MCF-7, in vivo. Vps34 inhibitor significantly potentiated cytotoxicity of Sunitinib and Erlotinib in MCF-7 and MDA-MB-231 in vitro in monolayer cultures and when grown as multicellular spheroids. Our data suggests that inhibition of autophagy significantly improves sensitivity to Sunitinib and Erlotinib and that Vps34 is a promising therapeutic target for combination strategies in breast cancer.