LMTK3 inhibitor C28 is a multi-kinase inhibitor.1 It inhibits lemur tyrosine kinase 3 (LMTK3), CDC-like kinase 2 (Clk2), dual-specificity tyrosine phosphorylation-regulated kinase 1α (DYRK1α), homeodomain-interacting protein kinase 2 (HIPK2), and IL-1 receptor-associated kinase 4 (IRAK4; IC50s = 67, 5, 6, 48, and 41 nM, respectively), among others. LMTK3 inhibitor C28 is selective for these kinases over a panel of 122 kinases at 1 ?M. It induces proteasomal degradation of LMTK3 in MCF-7, T47D, and MDA-MB-231 breast cancer cells when used at concentrations of 5 or 10 ?M. LMTK3 inhibitor C28 (10 ?M) reduces the levels of IRAK4, estrogen receptor α (ERα), phosphorylated tropomyosin-related kinase A (TrkA), and HIPK2 in T47D cells. It induces induces apoptosis in MCF-7, T47D, and MDA-MB-231 cells when used at a concentration of 10 ?M. In vivo, LMTK3 inhibitor C28 (10 mg/kg per day) reduces tumor growth and volume in an MDA-MB-231 mouse xenograft model.
References:
[1]. Ditsiou, A., Cilibrasi, C., Simigdala, N., et al.The structure-function relationship of oncogenic LMTK3Sci. Adv.6(46)eabc3099(2020).