JAK1
JAK1 is an essential Janus kinase that mediates biologic responses downstream of class II cytokine receptors, γc-containing receptors, and gp130-dependent receptors[1]. Mechanistically, the JAK/STAT pathway provides a rapid membrane-to-nucleus signaling module that drives transcriptional programs linked to inflammation, immunity, cancer, and autoimmune disease[2]. In inflammatory contexts, JAK1 transduces signals from γc cytokines, IL-6, interferons, and IL-10, connecting cytokine receptor activation to immune-cell regulation and synovial inflammation[3]. Disease models and human genetics support this role, because JAK1 gain-of-function variants drive immune dysregulation with atopic dermatitis, allergy, eosinophilia, and gastrointestinal inflammation[4][5]. Compared with related isoforms, JAK1 shows nonredundant signaling, and Jak1 has a dominant role over Jak3 in γc receptor signaling[1][6]. JAK2 more directly supports hematopoietic growth-factor pathways, whereas JAK3 is mainly linked to common γc receptor biology[3][6]. For experimental applications, selective JAK1 inhibitors help separate cytokine-driven inflammatory signaling from broader JAK blockade[7]. Chemical proteomics identified an allosteric cysteine in JAK1 C817, absent from JAK2 and JAK3, enabling inhibitors that block JAK1-dependent trans-phosphorylation and cytokine signaling[8].
References:
- [1]. Rodig SJ, et al. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell. 1998 May 1;93(3):373-83. [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]. Spinelli FR, et al. JAK1: Number one in the family; number one in inflammation? Rheumatology (Oxford). 2021 May 5;60(Suppl 2):ii3-ii10. [Content Brief]
- [4]. Del Bel KL, et al. JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome. J Allergy Clin Immunol. 2017 Jun;139(6):2016-2020.e5. [Content Brief]
- [5]. Fayand A, et al. Successful treatment of JAK1-associated inflammatory disease. J Allergy Clin Immunol. 2023 Oct;152(4):972-983. [Content Brief]
- [6]. Haan C, et al. Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors. Chem Biol. 2011 Mar 25;18(3):314-23. [Content Brief]
- [7]. Schwartz DM, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017 Dec;16(12):843-862. [Content Brief]
- [8]. Kavanagh ME, et al. Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine. Nat Chem Biol. 2022 Dec;18(12):1388-1398. [Content Brief]
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JAK1 Related Products (151)
Related Products (151)
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Recombinant Proteins (4)
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Antibodies (2)
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JAK1/3-IN-1
0 ImagesCat. No.: HY-123939CAS No.: 1400687-19-5JAK1/3-IN-1 is a selective, orally active JAK1/3 inhibitor with IC50 values of 1.9 nM and 0.9 nM, respectively. JAK1/3-IN-1 significantly reduces the mean arterial blood pressure and significantly increases the heart rate in rabbits. JAK1/3-IN-1 decreases the mean arterial blood pressure in conscious telemetered rats and induces lethal cardiovascular effects.
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Tofacitinib-13C
0 ImagesCat. No.: HY-40354S3Synonyms: Tasocitinib-13C; CP-690550-13CTofacitinib-13C (Tasocitinib-13C; CP-690550-13C) is the 13C-labeled Tofacitinib (HY-40354). Tofacitinib (Tasocitinib) is an orally active, blood-brain barrier permeable selective inhibitor of JAK1/JAK3. Tofacitinib blocks the JAK-STAT/NF-κB signaling pathway, inhibits cytokine signal transduction, phosphorylation of STAT1/STAT5, and suppresses innate and adaptive immune responses. Tofacitinib can be used in research related to major depressive disorder, rheumatoid arthritis, pulmonary diseases, systemic lupus erythematosus, and immune-mediated liver injury.
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Deuruxolitinib phosphate
0 ImagesCat. No.: HY-50856BSCAS No.: 2147706-60-1Synonyms: CTP-543 phosphate; Ruxolitinib-d8 phosphate; INCB18424-d8 (phosphaDeuruxolitinib phosphate (CTP-543 phosphate; Ruxolitinib-d8 phosphate) is a deuterated analog of Ruxolitinib (HY-50856) and an orally active, selective inhibitor of JAK1 and JAK2. Deuruxolitinib phosphate blocks Janus kinase-mediated cytokine receptor signaling and proinflammatory cytokine gene expression. Deuruxolitinib phosphate is primarily metabolized in the liver via CYP2C9. Deuruxolitinib phosphate promotes scalp hair regrowth in severe chronic alopecia areata. Deuruxolitinib phosphate is used in alopecia areata-related research.
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Domusiran
0 ImagesCat. No.: HY-185924CAS No.: 3077456-78-8Synonyms: ALY-101Domusiran (ALY-101) is a Jak-1 inhibitor.
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Tofacitinib-d3
0 ImagesCat. No.: HY-40354S5Synonyms: Tasocitinib-d3; CP-690550-d3Tofacitinib-d3 (Tasocitinib-d3; CP-690550-d3) is the deuterated-labeled Tofacitinib (HY-40354). Tofacitinib (Tasocitinib) is an orally active, blood-brain barrier permeable selective inhibitor of JAK1/JAK3. Tofacitinib blocks the JAK-STAT/NF-κB signaling pathway, inhibits cytokine signal transduction, phosphorylation of STAT1/STAT5, and suppresses innate and adaptive immune responses. Tofacitinib can be used in research related to major depressive disorder, rheumatoid arthritis, pulmonary diseases, systemic lupus erythematosus, and immune-mediated liver injury.
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Flonoltinib monomaleate
0 ImagesCat. No.: HY-130247BCAS No.: 3062214-21-2Synonyms: JAK2/FLT3-IN-1 monomaleate
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Momelotinib mesylate
0 ImagesCat. No.: HY-10963CAS No.: 1056636-07-7Synonyms: CYT387 mesylateMomelotinib mesylate (CYT387 mesylate) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3.
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ZM39923
0 ImagesCat. No.: HY-12589ACAS No.: 273727-89-2ZM39923 is a JAK3 inhibitor, with a pIC50 of 7.1; ZM39923 also potently inhibits tissue transglutaminase (TGM2) with an IC50 of 10 nM.
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AH057
0 ImagesCat. No.: HY-183519CAS No.: 118499-11-9AH057 is an orally active JAK1 and JAK2 inhibitor. AH057 blocks IL-6-, IFN-α- and IFN-γ-induced JAK/STAT signaling, reduces cancer cell proliferation, invasion and colony formation, and induces apoptosis and G1 cell-cycle arrest. AH057 can be used for cervical cancer research.
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AS2553627
0 ImagesCat. No.: HY-123187CAS No.: 1251906-10-1AS2553627 is a type of JAK inhibitor, with IC50 values of 0.46, 0.30, 0.14, and 2.0 nM for JAK1, JAK2, JAK3 and TYK2, respectively. AS2553627 can inhibit the proliferation of human and rat T cells stimulated by IL-2, with IC50 values of 2.4 and 4.3 nM, respectively. AS2553627 can reduce cardiac allograft vasculopathy and fibrosis in a rat heart transplant model, effectively extending survival rates. AS2553627 can be used to prevent acute and chronic rejection in heart transplants.
