Non-cytotoxic, potent and specific UNC119-cargo interation blocker that inhibits Lck localization at T-cell immune synpase and Src activation.

Squarunkin A is a non-cytotoxic, potent and specific UNC119-cargo interation blocker (IC50 = 10 nM against 800 nM myristoylated Src N-terminal peptide for GST-UNC119A) that targets UNC119A/B myristoyl-binding pocket without affecting the interaction of geranylgeranylated Rab1 to RhoGDI22, or farnesylated Rheb to PDE6d, AIPL1, and calmodulin. Squarunkin A blocks Lck localization at staphylococcal E enterotoxin-induced Jurkat T-cell synpase (2 μM) and prevents MDA-MB-231 cellular Src activation (37/62% reduced Src pY416 post 24 hr 78/625 nM Squarunkin A incubation) without growth inhibition or apoptosis induction (10 μM for >35 hrs).