Takinib

Takinib (EDHS-206) is an orally active and selective TAK1 inhibitor (IC₅₀=9.5 nM), more than 1.5 log more potent than the second and third ranked targets, IRAK4 (120 nM) and IRAK1 (390 nM), respectively. Takinib is an inhibitor of autophosphorylated TAK1 that non-competitively binds within the ATP binding pocket. Takinib induces apoptosis following TNFα stimulation in cell models of rheumatoid arthritis and metastatic breast cancer. Takinib is also a P. falciparum protein kinase 9 (PfPK9) inhibitor (K_D(app) of 0.46 μM)^[1][2][3]. IC50 & Target:IC50: 9.5 nM (TAK1); 120 nM (IRAK4); 390 nM (IRAK1); 450 nM (GCK) ^[1]
Apparent K_D: 0.46 μM (PfPK9)^[3] In Vitro: Takinib (10-10000 nM; 24 hours) induces apoptosis following TNF-α stimulation in MDA-MB-231 cells^[1].
Takinib (10 μM; 0-1 hours) reduces phosphorylation of IKK and p65^[1].
Takinib serves as a chemical starting point for the development of PfPK9 (K_D(app) of 0.46 μM) inhibitors for malaria^[3].
Takinib (2 hours; 0.1-20 µM; human RASFs) induces phosphorylation of TAK1^Thr184/187, STAT3^Tyr705 and STAT3^Ser727 in IL-1β-treated (10 ng/mL; 30 min) RASFs^[4]. In Vivo: Takinib (50 mg/kg; intraperitoneally; daily from days 18-36) reduces the clinical score in type II collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis^[4].
Takinib (50 mg/kg; oral gavage; daily until 17 days) slows tumor growth in the Hodgkin lymphoma xenograft NSG mice^[5].