JAK3
Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase of the JAK family that mediates cytokine receptor signaling and transduces extracellular immune signals through the JAK/STAT signaling pathway[1]. JAK3 functions downstream of cytokine receptors and participates in receptor-associated signaling events that regulate immune cell development, activation, and homeostasis through STAT phosphorylation and transcriptional regulation[1][2]. Mechanistically, cytokine-induced receptor dimerization activates JAK proteins, leading to receptor phosphorylation, STAT recruitment, STAT activation, and subsequent regulation of target gene expression involved in immunity and inflammatory responses[2][3]. In disease contexts, dysregulated JAK/STAT signaling is associated with immune-mediated disorders and inflammatory diseases, making JAK family members important therapeutic targets for pathway modulation[2][3]. Compared with the broadly expressed isoforms JAK1, JAK2, and TYK2, JAK3 exhibits a more restricted expression pattern and is primarily produced in hematopoietic and lymphoid cells, providing a key biological distinction among JAK family members[2][3]. This lineage-associated distribution links JAK3 more closely to adaptive immune regulation and supports its relevance in immune system research models[3]. For experimental applications, JAK3 has attracted substantial interest as a drug target because selective inhibition of cytokine-triggered JAK/STAT signaling can modulate immune responses while exploiting the relatively restricted cellular distribution of this isoform[3][4]. Consequently, the development of selective JAK3 inhibitors continues to provide valuable tools for investigating cytokine signaling mechanisms and immune-related disease biology[3][4].
Verweise:
- [1]. Kawamura M, et al. Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6374-8. [Content Brief]
- [2]. Hu X, et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021 Nov 26;6(1):402. [Content Brief]
- [3]. Kwon S. Molecular dissection of Janus kinases as drug targets for inflammatory diseases. Front Immunol. 2022 Dec 8;13:1075192. doi: 10.3389/fimmu.2022.1075192. PMID: 36569926; PMCID: PMC9773558. et al. Molecular dissection of Janus kinases as drug targets for inflammatory diseases. Front Immunol. 2022 Dec 8;13:1075192. [Content Brief]
- [4]. Chen C, et al. A highly selective JAK3 inhibitor is developed for treating rheumatoid arthritis by suppressing γc cytokine-related JAK-STAT signal. Sci Adv. 2022 Aug 19;8(33):eabo4363. [Content Brief]
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JAK3 Verwandte Produkte (141)
Verwandte Produkte (141)
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Ruxolitinib
0 ImagesSynonyms: INCB18424
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Tofacitinib
0 ImagesSynonyms: Tasocitinib; CP-690550Tofacitinib is an orally available JAK3/2/1 inhibitor with IC50s of 1, 20, and 112 nM, respectively.
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Upadacitinib
0 ImagesSynonyms: ABT-494Upadacitinib (ABT-494) is a potent, orally active and selective Janus kinase 1 (JAK1) inhibitor (IC50=43 nM). Upadacitinib (ABT-494) displays approximately 74 fold selective for JAK1 over JAK2 (200 nM) in cellular assays dependent on specific, relevant cytokines. Upadacitinib (ABT-494) can be used for several autoimmune disorders research.
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Baricitinib
0 ImagesSynonyms: LY3009104; INCB028050
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NUAK1-IN-3
0 ImagesArt. -Nr.: HY-182361CAS. Nr.: 3097515-05-1NUAK1-IN-3 is a potent and selective NUAK1 inhibitor with an IC50 of 0.49 nM. NUAK1-IN-3 also inhibits NUAK2 and JAK3 with IC50 values of 265 and 225 nM. NUAK1-IN-3 engages Glu139 of NUAK1, forms a salt bridge between its bicyclic ring nitrogen and Asp142, and uses a fluorine atom to enhance hydrophobic binding interactions. NUAK1-IN-3 attenuates MYPT1 phosphorylation, suppresses the NUAK1-MYPT1 signaling axis, and inhibits proliferation, migration, and invasion of triple-negative breast cancer cells. NUAK1-IN-3 reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) marker alterations, downregulates Snail and N-cadherin, and upregulates E-cadherin in tumor tissues. NUAK1-IN-3 suppresses tumor growth in triple-negative breast cancer xenograft models. NUAK1-IN-3 can be used for the research of triple-negative breast cancer.
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JAK3-IN-20
0 ImagesArt. -Nr.: HY-182314CAS. Nr.: 3104109-31-8JAK3-IN-20 is a selective and orally active JAK3 inhibitor with an IC50 of 0.7473 nM. JAK3-IN-20 forms a covalent bond with JAK3 Cys909, outcompetes ATP for catalytic site binding, and blocks JAK-STAT pathway activation. JAK3-IN-20 inhibits migration, proliferation, and tumor growth of Bortezomib (HY-10227)-resistant cancer cells. JAK3-IN-20 induces dose-dependent apoptosis. JAK3-IN-20 can be used for the research of Bortezomib-resistant multiple myeloma.
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Tubulosine
0 ImagesTubulosine is an alkaloid. Tubulosine can be isolated from Pogonopus tubulosus (DC.) Schumann. Tubulosine is an ATP-competitive, selective JAK3 inhibitor with an IC50 value of 9.9 nM. Tubulosine also inhibits the kinase activities of other JAK family members, the extent of inhibition is less than that of JAK3, with IC50 values of 69.5, 84.9 and 76.3 nM for JAK1, JAK2 and TYK2, respectively. Tubulosine selectively inhibits JAK3 signalling by binding to the ATP-binding site of the kinase of JAK3. Tubulosine induces apoptotic and necrotic/autophagic cell death. Tubulosine inhibits the process of peptide chain elongation by eukaryotic polysomes by, specifically preventing the elongation-factor-2-dependent step of translocation. Tubulosine exhibits anticancer activity in breast cancer cells.
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Tofacitinib citrate
0 ImagesSynonyms: Tasocitinib citrate; CP-690550 citrateTofacitinib citrate is an orally available JAK3/2/1 inhibitor with IC50s of 1, 20, and 112 nM, respectively. Tofacitinib citrate has antibacterial, antifungal and antiviral activities.
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Ritlecitinib
0 ImagesSynonyms: PF-06651600Ritlecitinib (PF-06651600) is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC50=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC50 >10 μ M). Ritlecitinib rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).
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Filgotinib
0 ImagesSynonyms: GLPG0634Filgotinib (GLPG0634) is a selective, orally available JAK1 inhibitor with anti-inflammatory and antiviral activities. Filgotinib can effectively inhibit the activities of JAK1, JAK2, JAK3 and TYK2 with IC50 values of 10 nM, 28 nM, 810 nM and 116 nM, respectively. Filgotinib also inhibits HIV-1 driven gene transcription and reduces proliferation of HIV-1 infected cells. Filgotinib can be used in the study of rheumatoid arthritis and inflammatory bowel disease.
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Baricitinib phosphate
0 ImagesSynonyms: LY3009104 phosphate; INCB028050 phosphate
