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ID-8 is a small molecule inhibitor of DYRK [1].

Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) is an enzyme that catalyzes autophosphorylation on tyrosine and serine/threonine residues.

ID-8 is a small molecule DYRK inhibitor. In HES2 cells, ID-8 (0.5 μM) increased hESC survival by 1.1%. The combination of ID-8 and Wnt3a increased survival by 1.7% and completely inhibited Wnt-induced morphological differentiation. Also, ID-8 significantly reduced the expression of differentiation marker gene GATA6, GSC, SOX17 and CDX2 induced by Wnt. In hESCs, ID-8 increased Wnt-mediated hESC proliferation and survival via inhibition of DYRKs. Also, DYRK family is direct targets of ID-8 [1]. In embryonic stem cells (ESCs), ID-8 (10 μM) stimulated proliferation in culture without MEFs, serum or LIF. The ID-8 induced ESCs showed the ability to form all three germ layer-derived tissues, such as liver, neurons and muscles. Also, ID-8 increased ESC differentiation and the levels of Nanog, Sox2 and Rex-1 [2]. In mouse ESCs cultured in serum-free medium, ID-8 maintained their self-renewal and pluripotency [3].

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