4py1
From Proteopedia
Crystal structure of Tyk2 in complex with compound 15, 6-((2,5-dimethoxyphenyl)thio)-3-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine
Structural highlights
DiseaseTYK2_HUMAN Mendelian susceptibility to mycobacterial diseases;Autosomal recessive hyper IgE syndrome. Defects in TYK2 are the cause of protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:611521; also known as autosomal recessive hyper-IgE syndrome (HIES) with atypical mycobacteriosis. TYK2 deficiency consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. FunctionTYK2_HUMAN Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.[1] Publication Abstract from PubMedLeucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD). The most common mutant, G2019S, increases kinase activity, thus LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the structure, potential ligand-protein binding interactions, and pharmacological profiling of potent and highly selective kinase inhibitors based on a triazolopyridazine chemical scaffold. Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold.,Galatsis P, Henderson JL, Kormos BL, Han S, Kurumbail RG, Wager TT, Verhoest PR, Noell GS, Chen Y, Needle E, Berger Z, Steyn SJ, Houle C, Hirst WD Bioorg Med Chem Lett. 2014 Sep 1;24(17):4132-40. doi: 10.1016/j.bmcl.2014.07.052., Epub 2014 Jul 30. PMID:25113930[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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