Novel methods for the treatment of inflammatory and autoimmune diseases comprising the administration of salt-inducible kinase inhibitors are claimed. One novel inhibitor (HG-9-91-01) and the use of 2,4-diaminopyrimidine and 2,6-diaminopyrimidine derivatives are claimed. The use of such inhibitors upregulates the level of the anti-inflammatory cytokine IL-10 in macrophages.
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http://dx.doi.org/10.1517/13543776.2014.908851 | DOI Listing |
Resistance to radiotherapy remains a critical barrier in treating colorectal cancer (CRC), particularly in cases of locally advanced rectal cancer (LARC). To identify key kinases involved in CRC radioresistance, we employed a kinase-targeted CRISPR-Cas9 library screen. This approach aimed to identify potential kinase inhibitors as radiosensitizers.
View Article and Find Full Text PDFSAR QSAR Environ Res
December 2024
Structural Biology and Biocomputing Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India.
Diabetes mellitus (DM) affects over 77 million adults in India, with cases expected to reach 134 million by 2045. Current treatments, including sulfonylureas and thiazolidinediones, are inadequate, underscoring the need for novel therapeutic strategies. This study investigates marine natural products (MNPs) as alternative therapeutic agents targeting SIK2, a key enzyme involved in DM.
View Article and Find Full Text PDFCell Chem Biol
January 2025
Laboratory of Neurochemical Biology, Peking-Tsinghua Center for Life Sciences, Peking-Tsinghua-NIBS (PTN) Graduate Program, School of Life Sciences, Peking University, Beijing, China; Chinese Institute for Brain Research (CIBR), Beijing, China; Department of Chemical Biology, College of Chemistry and Chemical Engineering; School of Pharmaceutical Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Chinese Institutes for Medical Research (CIMR), Beijing, China; Capital Medical University, Beijing, China. Electronic address:
Research into mechanisms underlying sleep traditionally relies on electrophysiology and genetics. Because sleep can only be measured on whole animals by behavioral observations and physical means, no sleep research was initiated by biochemical and chemical biological approaches. We used phosphorylation sites of kinases important for sleep as targets for biochemical and chemical biological approaches.
View Article and Find Full Text PDFDrug Discov Today
December 2024
Cell Signaling and Cancer Biology Laboratory, Department of Biochemistry, Guindy Campus, University of Madras, Chennai 600025, India. Electronic address:
Salt-inducible kinases (SIKs), a group of serine/threonine kinases in the adenosine monophosphate-activated protein kinase (AMPK) family, exist in three isoforms: SIK1, SIK2 and SIK3. These kinases are crucial in various physiological processes. Emerging evidence indicates that dysregulation of SIK expression and activation significantly contributes to carcinogenesis by promoting cellular proliferation, metabolic dysregulation, metastasis and chemoresistance through the modulation of crucial signaling pathways.
View Article and Find Full Text PDFSleep
December 2024
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.
Study Objectives: Sleep/wakefulness is regulated by intracellular signaling pathways composed of protein kinases such as salt-inducible kinase 3 (Sik3). Sik3-deficiency in neurons decreases NREM sleep time and electroencephalogram (EEG) delta power during NREM sleep, while Sik3Slp mice lacking a protein kinase A (PKA)-phosphorylation site, S551, show hypersomnia phenotype. In this study, we examined how a phosphomimetic mutation of the 221st threonine residue (T221E), which provides a partial (weak) constitutive activity of the kinase, affects sleep/wakefulness and circadian behavior.
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