Longdaysin

Longdaysin (CAS No.: 1353867-91-0) is a small-molecule kinase inhibitor widely used in chemical biology and drug discovery research as a modulator of circadian rhythms and Wnt/β-catenin signaling. It functions primarily through inhibition of casein kinase 1 isoforms, including CK1α and CK1δ, and also exhibits activity against additional kinases such as CDK7, ERK2, and related kinases, with inhibitory effects generally observed in the low to mid micromolar range. Mechanistically, Longdaysin suppresses CK1-dependent phosphorylation events, leading to attenuation of Wnt/β-catenin pathway activation, reduced phosphorylation of upstream components such as LRP6 and DVL2, and decreased levels of active and total β-catenin, thereby downregulating transcription of Wnt target genes including Axin2, DKK1, LEF1, and Survivin. In cellular systems, it has been shown to extend circadian period length and inhibit Wnt3A-induced signaling, while in cancer models, particularly breast cancer cell lines such as Hs578T and MDA-MB-231, it reduces proliferation, migration, invasion, and colony formation. In vivo studies using xenograft models further demonstrate its ability to suppress tumor growth in association with Wnt pathway inhibition. Longdaysin is therefore a valuable tool compound for investigating kinase-regulated signaling networks, circadian biology, and oncogenic Wnt signaling, with experimental concentrations and dosing regimens varying depending on the specific biological context and study design.