TH470represents an adduct of the canonical type I inhibitor LIMKi3 andthe αC-out and DFG-out inhibitor TH257 resulting in a highlypotent and selective chemical probe that have been demonstrated tobe efficacious in cellular models of LIMK1-associated diseases suchas Fragile X syndrome caused by loss-of-function mutation of the fragileX mental retardation 1 (FMR1) gene.26 Comparison of the inactive states of RIPK1 and LIMK αC-outand DFG-out conformation suggests that the benzoxazepinone scaffoldcould be adapted inhibiting also LIMK1/2. The gene discussed is LIMK1; the disease is fragile X syndrome.