Adavivint

Adavivint is an inhibitor of Wnt signaling (EC50 = 19. nM in a reporter assay using SW480 cells). It inhibits CMGC family kinases, including CDC-like kinase 2 (Clk2) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A, IC50s = 7. and 26. nM, respectively), as well as Clk1, Clk3, Clk4, DYRK1B, glycogen synthase kinase 3beta (GSK3beta), and homeodomain-interacting protein kinase 1 (HIPK1), HIPK2, and HIPK3 (IC50s = 16.8-239 nM). Adavivint also induces activation of YES-associated transcriptional regulator (YAP) in a reporter assay using HEK293A cells (EC50 = 1. nM) in a Clk2-dependent manner. It induces chondrogenesis in primary human bone marrow-derived mesenchymal stem cells (MSCs). Adavivint inhibits the replication of pseudorabies virus in infected HeLa, BHK-21, Vero, and PK(15) cells (IC50s = 0. 0. 0. and 0. µM, respectively). Intra-arterial administration of adavivint (0. µg/animal) decreases disease severity in a surgically induced rat model of osteoarthritis. Adavivint (50 mg/kg) also inhibits tumor growth in a patient-derived organoid xenograft mouse model of colorectal cancer. InChI: InChI=1S/C29H24FN7O/c1-16(2)8-26(38)33-21-10-19(12-31-13-21)17-6-7-24-22(11-17)28(37-36-24)29-34-25-15-32-14-23(27(25)35-29)18-4-3-5-20(30)9-18/h3-7,9-16H,8H2,1-2H3,(H,33,38)(H,34,35)(H,36,37) InChIKey: AQDWDWAYVBQMAM-UHFFFAOYSA-N SMILES: O=C(CC(C)C)NC1=CC(C2=CC3=C(C=C2)NN=C3C4=NC5=C(N4)C(C6=CC(F)=CC=C6)=CN=C5)=CN=C1