N-Desmethyl imatinib

N‑Desmethyl imatinib (Norimatinib) is an active metabolite of Imatinib (HY-15463), a selective c‑Abl inhibitor, and a substrate of P‑glycoprotein. N-Desmethyl imatinib binds to the c-Abl catalytic domain to prevent substrate phosphorylation, inhibits c-Abl-mediated α-synuclein activation and downstream inflammatory signaling pathways. N-Desmethyl imatinib induces apoptosis in K562 human leukemia cells. N-Desmethyl imatinib shows significantly elevated plasma levels in gastrointestinal stromal tumor (GIST) models with mild SARS-CoV-2 infection. N-Desmethyl imatinib can be used for the research of Parkinson’s disease, gastrointestinal stromal tumor, and chronic myeloid leukemia^[1][2][3]. In Vitro:N-Desmethyl imatinib (CGP 74588) (0.3-30 μM) acts as a substrate for P-glycoprotein, stimulating ATPase activity in P-glycoprotein-expressing Sf9 cell membrane vesicles at concentrations ranging from 0.3 to 30 μM^[3].
N-Desmethyl imatinib (48 h) inhibits K562 cell proliferation with an IC₅₀ of 0.58 μM and shows no significant inhibition of K562/Dox cell proliferation (IC₅₀ > 20 μM) after 48 h of treatment^[3].
N-Desmethyl imatinib (1.6 μM, 20 μM; 48 h) induces apoptosis in K562 cells, but does not significantly induce apoptosis in K562/Dox cells^[3].