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].
References:
- [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]
-
JAK3 Related Products (158)
Related Products (158)
-
JAK1/TYK2-IN-3
0 ImagesCat. No.: HY-143885CAS No.: 2734918-37-5JAK1/TYK2-IN-3 is a potent, selective and orally active dual TYK2/JAK1 inhibitor with IC50 values of 6 and 37 nM, respectively. JAK1/TYK2-IN-3 also shows selectively relative to JAK2 (IC50=140 nM) and JAK3 (IC50=362 nM). JAK1/TYK2-IN-3 shows anti-inflammatory effect by regulating the expression of related TYK2/JAK1-regulated genes, as well as the formation of Th1, Th2, and Th17 cells.
-
JAK3-IN-20
0 ImagesCat. No.: HY-182314CAS No.: 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.
-
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.
-
TYK2 activator-2
0 ImagesCat. No.: HY-187211TYK2 activator-2 (Compound 6g) is a selective TYK2 activator and JAK3 inhibitor, with an EC50 of 0.21 μM against TYK2 and an IC50 of 1.2 μM against JAK3. TYK2 activator-2 destabilizes the JH2-JH1 autoinhibitory complex of TYK2, enhances the catalytic activity of TYK2, and inhibits the JH1 kinase domain activity of JAK3. TYK2 activator-2 can be used in cancer-related research.
-
JAK3-IN-9
0 ImagesCat. No.: HY-133747CAS No.: 1430095-30-9JAK3-IN-9 is an orally active JAK3 inhibitor with IC50 value of 1.7 nM. JAK3-IN-9 is highly selective to the JAK3 signal path. JAK3-IN-9 is lowly toxic with high oral bioavailability, shows good anti-arthritis activity. JAK3-IN-9 can be used in autoimmune disease research.
-
JAK3-IN-11
0 ImagesCat. No.: HY-146727CAS No.: 2412734-00-8JAK3-IN-11 (Compound 12), a potent, noncytotoxic, irreversible, orally active JAK3 inhibitor with IC50 value of 1.7 nM, has excellent selectivity (>588-fold compared to other JAK isoforms), covalently bind to the ATP-binding pocket in JAK3. JAK3-IN-11 strongly inhibits JAK3-dependent signaling and T cell proliferation, is a promising tool for study autoimmune diseases.
-
JAK-2/3-IN-2
0 ImagesCat. No.: HY-151256CAS No.: 2170398-48-6
-
Envudeucitinibum hydrochloride
0 ImagesCat. No.: HY-153701S1CAS No.: 3009133-87-0Synonyms: Envudeucitinib hydrochloride; ESK-001 hydrochlorideEnvudeucitinibum (Envudeucitinib; ESK-001) hydrochloride is an orally active and selective TYK2 allosteric inhibitor with an IC50 range of 104-149 nM. Envudeucitinibum hydrochloride blocks JH1 catalytic activity by specifically binding to the JH2 domain of TYK2, thereby inhibiting downstream signaling pathways. Envudeucitinibum hydrochloride is used for research on plaque psoriasis, systemic lupus erythematosus, and other immune-mediated diseases.
-
DPPY
0 ImagesCat. No.: HY-147741CAS No.: 2095883-62-6
-
Embricitinib
0 ImagesCat. No.: HY-176793CAS No.: 2459377-98-9Synonyms: JAK1-IN-18Embricitinib (JAK1-IN-18) (Example 2) is a selective JAK1 inhibitor with an IC50 of 0.15 nM for JAK1 over JAK2 and JAK3. Embricitinib significantly reduces inflammation in DSS (HY-116282C)-induced ulcerative colitis (UC) mouse models and DNBS(HY-W324435)-induced Crohn's disease (CD) rat models. Embricitinib can be used for autoimmune diseases (such as inflammatory bowel disease), viral infections (such as HBV infection) and cancers (such as blood cancer) research.
-
IRAK4-IN-35
0 ImagesCat. No.: HY-187692CAS No.: 3112339-39-3IRAK4-IN-35 is an orally active IRAK4 inhibitor with an IRAK4 IC50 of 9.88 nM. IRAK4-IN-35 also inhibits JAK3, EGFR, CDK2 with IC50 values of 6.72 nM, 32.35 nM, and 39.08 nM, respectively. IRAK4-IN-35 inhibits the production of proinflammatory cytokines, blocks inflammatory signaling pathways, and reduces serum TNF-α levels and spleen index in mouse models of acute inflammation. IRAK4-IN-35 decreases the disease activity index, paw swelling degree, and spleen index in a collagen-induced arthritis mouse model. IRAK4-IN-35 can be used for the research of rheumatoid arthritis.
-
Durocitinib
0 ImagesCat. No.: HY-187865SCAS No.: 2821087-28-7Durocitinib is a potent and selective TYK2 inhibitor. Durocitinib exhibits anti-inflammatory and immunosuppressive effects. Durocitinib can be used in research on autoimmune and inflammatory diseases.
-
Tyk2-IN-28
0 ImagesCat. No.: HY-187467Tyk2-IN-28 is an orally active and selective TYK2 inhibitor with an IC50 of 0.9 nM. Tyk2-IN-28 also inhibits JAK2 kinase activity with an IC50 of 4 nM. Tyk2-IN-28 blocks inflammatory cytokine signaling. Tyk2-IN-28 reduces paw swelling in mouse models. Tyk2-IN-28 can be used for research on psoriasis.
-
WWQ-131
0 ImagesCat. No.: HY-174430CAS No.: 1558007-80-9WWQ-131 is a potent selective JAK2 inhibitor with an IC50 of 2.56 nM. WWQ-131 shows >252-fold selectivity over JAK1, JAK3, and TYK2. WWQ-131 exhibits antiproliferative activity against cancer cells. WWQ-131 is the ligand for target protein for PROTAC JAK2 degrader-1 (HY-174428). WWQ-131 can be used for the research of myeloproliferative neoplasms (MPNs).
