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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Deuruxolitinib
0 ImagesSynonyms: CTP-543; Ruxolitinib-d8; INCB18424-d8Deuruxolitinib (CTP-543; Ruxolitinib-d8) is a deuterated analog of Ruxolitinib (HY-50856) and an orally active, selective inhibitor of JAK1 and JAK2. Deuruxolitinib blocks Janus kinase-mediated cytokine receptor signaling and proinflammatory cytokine gene expression. Deuruxolitinib is primarily metabolized in the liver via CYP2C9. Deuruxolitinib promotes scalp hair regrowth in severe chronic alopecia areata. Deuruxolitinib is used in alopecia areata-related research.
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JAK-IN-23
0 ImagesJAK-IN-23 is an orally active double inhibitor of JAK/STAT and NF-κB. JAK-IN-23 can inhibit JAK1/2/3 with IC50 values of 8.9 nM, 15 nM and 46.2 nM, respectively. JAK-IN-23 has potent inhibitory activities against interferon-stimulated genes (ISG) and NF-κB pathways with IC50 values of 3.3 nM and 150.7 nM, respectively. JAK-IN-23 has great anti-inflammatory that decreases the release of various proinflammatory factors. JAK-IN-23 can be used for the research of inflammatory bowel disease (IBD).
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ZM39923 hydrochloride
0 ImagesZM39923 hydrochloride is a JAK3 inhibitor, with a pIC50 of 7.1; ZM39923 hydrochloride also potently inhibits tissue transglutaminase (TGM2) with an IC50 of 10 nM.
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Graveoline
0 ImagesGraveoline (Rutamine) is an orally active alkaloid with various activities such as antifungal, antiparasitic, anti-inflammatory, and antitumor effects. Graveoline can induce tumor cell apoptosis and autophagy through a reactive oxygen species-mediated pathway. Graveoline has an MIC of 500 μg/mL for Candida albicans. Graveoline can be used in the research of various diseases such as tumors and liver injury.
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HG-7-85-01
0 ImagesHG-7-85-01 is a type II ATP competitive inhibitor of wild-type and gatekeeper mutations forms of Bcr-Abl, PDGFRα, Kit, and Src kinases. HG-7-85-01 inhibits T315I mutant Bcr-Abl kinase, KDR and RET with IC50s of 3 nM, 20 nM and 30 nM, and is only weak or no inhibition of other kinases (IC50>2 μM). HG-7-85-01 inhibits the cell proliferation, which is mediated by the induction of apoptosis, and inhibition of cell-cycle progression.
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Envudeucitinibum
0 ImagesSynonyms: Envudeucitinib; ESK-001Envudeucitinibum (Envudeucitinib; ESK-001) is an orally active and selective TYK2 allosteric inhibitor with an IC50 range of 104-149 nM. Envudeucitinibum blocks JH1 catalytic activity by specifically binding to the JH2 domain of TYK2, thereby inhibiting downstream signaling pathways. Envudeucitinibum is used for research on plaque psoriasis, systemic lupus erythematosus, and other immune-mediated diseases.
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Filgotinib maleate
0 ImagesSynonyms: GLPG0634 maleateFilgotinib maleate (GLPG0634 maleate) is a selective, orally available JAK1 inhibitor with anti-inflammatory and antiviral activities. Filgotinib maleate 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 maleate also inhibits HIV-1 driven gene transcription and reduces proliferation of HIV-1 infected cells. Filgotinib maleate can be used in the study of rheumatoid arthritis and inflammatory bowel disease.
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3',4'-Dihydroxyflavone
0 Images3',4'-Dihydroxyflavone is an orally active antioxidant. 3',4'-Dihydroxyflavone inhibits the NF-κB, JAK1/STAT1, AP-1, IRF3, and MAPK/MEK/ERK pathways, while activating Nrf2 and reducing Keap1, thereby exerting anti-inflammatory and antioxidant effects. 3',4'-Dihydroxyflavone inhibits NO, PGE2, pro-inflammatory cytokines, and ROS production, upregulates GSH, and activates KATP channels, adenosine A3 receptors, and GABAA receptors. 3',4'-Dihydroxyflavone inhibits PPARγ expression and adipogenic differentiation, induces osteogenic differentiation; it also inhibits 5-lipoxygenase and xanthine oxidase, weakly inhibits PARP1, and scavenges DPPH and superoxide radicals. 3',4'-Dihydroxyflavone can be used for research on peripheral nerve injury, septic shock, obesity, influenza A virus infection, infertility, and diabetic complications.
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Quecitinib
0 ImagesSynonyms: QY201Quecitinib (QY201) is an orally active JAK1/TYK2 dual inhibitor. Quecitinib is also a substrate of cytochrome P450 3A and is mainly metabolized to mono-oxide and glucuronidation products. Quecitinib has favorable pharmacokinetic properties as well as safety. Quecitinib can be used in the research of atopic dermatitis and other autoimmune diseases.
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Tofacitinib-13C3
0 ImagesSynonyms: Tasocitinib-13C3; CP-690550-13C3Tofacitinib-13C3 (Tasocitinib-13C3; CP-690550-13C3) 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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Cerdulatinib hydrochloride
0 ImagesSynonyms: PRT062070 hydrochloride; PRT2070 hydrochlorideCerdulatinib hydrochloride (PRT062070) is a selective, oral active and reversible ATP-competitive inhibitor of dual SYK and JAK, with IC50s of 32 nM, 0.5 nM, 12 nM, 6 nM and 8 nM for SYK and Tyk2, JAK1, 2, 3, respectively. Cerdulatinib hydrochloride could be used to research autoimmune disease and B-cell malignancies.
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JAK2-IN-7
0 ImagesJAK2-IN-7 is a selective JAK2 inhibitor with IC50s of 3, 11.7, and 41 nM for JAK2, SET-2, and Ba/F3V617F cells, respectively. JAK2-IN-7 possesses >14-fold selectivity over JAK1, JAK3, FLT3. JAK2-IN-7 stimulates cell cycle arrest in the G0/G1 phase and induces tumor cellapoptosis. Antitumor activities.
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Ilginatinib hydrochloride
0 ImagesSynonyms: NS-018 hydrochloride
![Methyl 6-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-4-oxo-4,5-dihydropyrazolo[1,5-a]pyrazine-2-carboxylate](https://file.medchemexpress.com/product_pic/hy-153440.gif "Click to View Methyl 6-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-4-oxo-4,5-dihydropyrazolo[1,5-a]pyrazine-2-carboxylate Product Detail")
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GS-829845
0 ImagesGS-829845 is a is a major, active metabolite of Filgotinib (HY-18300). GS-829845 is a JAK1 preferential inhibitor but is approximately 10-fold less potent than the parent and with a longer half-life.
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(R,R)-VVD-118313
0 Images(R,R)-VVD-118313 is the isomer of VVD-118313 (HY-151385). VVD-118313 is a selective JAK1 inhibitor and blocks JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 can be used for research of cancer. (R,R)-VVD-118313 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
