SP98

SP98 is a novel, target-selective small molecule modulator of Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) signaling. Developed by researchers at the University of Maryland and Thomas Jefferson University, SP98 is designed to overcome the off-target effects associated with traditional ATP-competitive ERK inhibitors. It functions by binding to the F-site recruitment site (FRS), a substrate-binding domain on ERK2, thereby selectively inhibiting the activation of specific downstream targets like the Activator Protein-1 (AP-1) transcription factor complex. In preclinical models of asthma, SP98 has demonstrated the ability to attenuate airway smooth muscle (ASM) cell proliferation and reduce the expression of α-smooth muscle actin (α-SMA) and Cyclin D1 without significant cytotoxicity. This substrate-selective approach aims to target airway remodeling in chronic asthma while maintaining broader cellular homeostasis.