Risvodetinib (IkT-148009) is an orally active, selective and brain-penetrant protein tyrosine kinase inhibitor, displaying excellent target efficacy against c-Abl1, c-Abl2/Arg with IC50 values of 33 nM, 14 nM, respectively. Risvodetinib suppresses c-Abl activation and substantially protects dopaminergic neurons from degeneration in mouse models of both inherited and sporadic Parkinson’s disease (PD), which is promising for research in the field of PD.
Risvodetinib (100 mg/kg, p.o., daily for 10 days) performs robust functional rescue and significant protection of dopaminergic (DA) neurons in the MPTP acute neurotoxicity mouse model[1].Risvodetinib (50 or 100 mg/kg, p.o., daily for 8 or 20 weeks) recovers nigrostriatal neurodegeneration and reduces phosphorylated α-synuclein in the mouse model of inherited PD[1].Risvodetinib (100 mg/kg, p.o., once a day, 5 times per week for 6 months) has an effective neuroprotection and reduces α-synuclein pathology in mouse model of sporadic PD[1].Pharmacokinetics of IkT-148009 in mouse plasma and brain[1]
References:
[1]. Karuppagounder SS, et al. The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson's disease. Sci Transl Med. 2023 Jan 18;15(679):eabp9352.
[2]. Werner MH, et al. Preparation of N-[3-[[4-(2-pyridyl)pyrimidin-2-yl]amino]phenyl]-4-[(piperazin-1-yl)metl]benzamide derivatives as inhibitors of kinases: World Intellectual Property Organization, WO2016172528. 2016-10-27. [3]. WHO Drug Information-World Health Organization (WHO). [4]. Werner MH, Olanow CW. Parkinson's Disease Modification Through Abl Kinase Inhibition: An Opportunity[J]. Mov Disord. 2022 Jan;37(1):6-15.