K 02288

K02288 is a potent inhibitor of ALK, and inhibits ALK1/2/3/6 with IC50s of 1.8/1.1/34.4/6.3 nM; K02288 is less potent against ALK4/5, with IC50s of 302 nM and 321 nM.

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> ALK

Signaling Pathways >> TGF-beta/Smad >> TGF-β Receptor

Research Areas >> Others

IC50：1.8 nM (ALK1), 1.1 nM (ALK2), 34.4 nM (ALK3), 6.3 nM (ALK6), 302 nM (ALK4), 321 nM (ALK5)[1]

K02288 reduces a robust phosphorylation of Smad1/5/8 induced by BMP4 stimulation, with an apparent IC50 of 100 nM. K02288 causes near complete inhibition of Smad2 phosphorylation at 0.5 µM[1]. K02288 binds to ALK1 in an ATP-mimetic fashion with two hydrogen bonds to the kinase hinge. K02288 also inhibits BMP9-ALK1 signalling, and induces a hypersprouting phenotype in HUVECs[2].

K02288 (1 µM) induces dysfunctional angiogenesis in a chick embryo CAM model[2].

[1]. Sanvitale CE, et al. A new class of small molecule inhibitor of BMP signaling. PLoS One. 2013 Apr 30;8(4):e62721.

[2]. Kerr G, et al. A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis. Angiogenesis. 2015 Apr;18(2):209-17.

SB431542 | Galunisertib (LY2157299) | A 83-01 | Brigatinib | LY2109761 | lorlatinib | LDN193189 | Alectinib (CH5424802) | RepSox | Entrectinib | SB525334 | Vactosertib (TEW-7197) | DMH-1 | GW788388 | LY364947