Definition
ChEBI: HG-9-91-01 is a member of the class of phenylureas that is a potent inhibitor of salt-inducible kinase 2, a potential target protein for therapy in ovarian cancer. It has a role as an antineoplastic agent and a salt-inducible kinase 2 inhibitor. It is a dimethoxybenzene, an aminopyrimidine, a N-arylpiperazine, a N-alkylpiperazine, a secondary amino compound and a member of phenylureas.
Biological Activity
hg-9-91-01 is a pan-sik (salt-inducible kinases) inhibitor with ic50 values of 0.92nm, 6.6nm and 9.6nm for sik1, sik2, sik3, respectively [1].siks restrict the formation of regulatory macrophages. the inhibition of these enzymes is thought to have potential for treating inflammatory and autoimmune diseases. hg-9-91-01 potently inhibits siks through targeting both the atp-binding site and the small hydrophobic pocket. it is reported that, besides siks, hg-9-91-01 also inhibits various protein tyrosine kinases such as src, btk, fgf and ephrin receptors. but other ampk-related kinase subfamily members are not sensitive to hg-9-91-01. hg-9-91-01 can promote lps-stimulated il-10 production, creb-dependent gene transcription, inhibit proinflammatory cytokine secretion and induce the expression of regulatory macrophage markers [1].
References
[1] clark k, mackenzie k f, petkevicius k, et al. phosphorylation of crtc3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. proceedings of the national academy of sciences, 2012, 109(42): 16986-16991.
