IkT-148009 (Risvodetinib, IkT09) is a potent, selective, orally bioavailable and brain-penetrant c-Abl inhibitor with IC50 of 33 and 14 nM for c-Abl (Abl1) and its closely related isoform c-Abl2 (Arg), respectively.
IkT-148009 shows little to know inhibition against the other members of the c-Abl family, c-Kit, PDGFRα, and PDGFRβ with IC50 of 2975, 1009 and 881 nM, respectively.
IkT-148009 (100 mg/kg per day) suppressed c-Abl activation in the mouse brains of MPTP-treated mice.
IkT-148009 showed protection from degeneration of nigrostriatal DA neurons in mouse brain in MPTP neurotoxicity mouse model of parkinson's disease (PD), significantly reduced the MPTP-induced loss of dopamine and the loss of the DA metabolites, 3-4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3-methoxytyramine (3MT).
IkT-148009 (100 mg/kg per day, 1% HPMC (hydroxypropyl methylcellulose), 1% Tween 80, and 10% PEG 400 in sterile water, oral gavage) rescued DA neuron loss, reduced pathological α-synuclein inmouse model of inherited and sporadic PD.