IGS-2.7 is a potent, selective and brain permeable CK1delta (CK-1δ, CK1δ) inhibitor with IC50 of 23 nM, >35-fold selective over CK1ε (IC50=840 nM). IGS-2.7 decreases TDP-43 phosphorylation and nuclear localization using a cell-based model of human lymphoblast from FTD patients carrying a progranulin (GRN) mutation。 IGS-2.7 produces a significant preservation of motor neurons in the anterior horn at lumbar level, a decrease in both astroglial and microglial reactivity in this area, and in TDP-43 phosphorylation in spinal cord samples. IGS-2.7 recoveredTDP-43 homeostasis (phosphorylation and localization) in a human-based cell model from ALS patients.
