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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Itacitinib adipate
0 ImagesSynonyms: INCB039110 adipateItacitinib adipate (INCB039110 adipate) is an orally active JAK1-selective inhibitor. Itacitinib adipate inhibits IFN-γ-mediated phosphorylation of STAT1 and downstream pro-inflammatory signaling pathways. Itacitinib adipate reduces the frequency and number of splenic neutrophils in mouse models, downregulates the levels of pro-inflammatory cytokines and chemokines, and inhibits pro-inflammatory gene expression pathways. Itacitinib adipate improves survival rate and clinical scores in mouse models of hemophagocytic lymphohistiocytosis (HLH), and also suppresses metastasis in NSCLC models with high Rab1A expression. Itacitinib adipate can be used for research on hemophagocytic lymphohistiocytosis and non-small cell lung cancer.
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MJ04
0 ImagesMJ04 is a selective inhibitor for Janus Kinase 3 (JAK 3) with an IC50 of 2.03 nM. MJ04 inhibits T cell differentation and inhibits the proinfammatory cytokines in Lipopolysaccharides (HY-D1056)‑induced macrophages. MJ04 exhibits good pharmacokinetic characters in mice, promotes hair growth in DHT-induced androgenetic alopecia (AGA) in athymic mice model, without significant toxicity (LD50 >2 g/kg).
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Dual Cathepsin L/JAK-IN-1
0 ImagesDual Cathepsin L/JAK-IN-1 (Compound A8) is a dual inhibitor of Cathepsin L (CTSL) and JAK, with IC50 values of 0.68 μM, 337.1 nM, 5.251 nM, 27.29 nM, and 172.6 nM for CTSL, JAK1/2/3, and TYK2, respectively. Dual Cathepsin L/JAK-IN-1 effectively blocks the activation of the MAPK, NF-κB, and JAK/STAT signaling pathways, leading to significant anti-inflammatory therapeutic effects. Dual Cathepsin L/JAK-IN-1 can be used in research on acute lung injury (ALI).
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Ruxolitinib sulfate
0 ImagesCat. No.: HY-50859CAS No.: 1092939-16-6Synonyms: INCB018424 sulfateRuxolitinib sulfate (INCB018424 sulfate) is the first potent, selective JAK1/2 inhibitor to enter the clinic with IC50s of 3.3 nM/2.8 nM, and has > 130-fold selectivity for JAK1/2 versus JAK3.
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Leucrose
0 ImagesLeucrose (5-O-α-D-Glucopyranosyl-D-fructose) is an orally active Sucrose (HY-B1779) isomer naturally found in pollen and honey. Leucrose promotes phosphorylation of JAK1 and STAT6, reduces pro-inflammatory mediators and cytokinesas (TNFα, and IL-1β), increases M2 macrophage polarization and suppresses DSS (HY-116282C)-induced colitis. Leucrose suppresses hepatic triglyceride accumulation, improves fasting blood glucose levels, and regulates hepatic lipogenesis and fatty acid β-oxidation in high-fat diet-induced obese mice. Leucrose is slowly hydrolyzed into glucose and fructose by α-glucosidase and acts as as a sugar substitute in diet.
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Upadacitinib tartrate tetrahydrate
0 ImagesCat. No.: HY-19569ACAS No.: 1607431-21-9Synonyms: ABT-494 tartrate tetrahydrateUpadacitinib (ABT-494) tartrate tetrahydrate is a potent, orally active and selective Janus kinase 1 (JAK1) inhibitor (IC50=43 nM). Upadacitinib tartrate tetrahydrate displays approximately 74 fold selective for JAK1 over JAK2 (200 nM) in cellular assays dependent on specific, relevant cytokines. Upadacitinib tartrate tetrahydrate can be used for several autoimmune disorders research.
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RAI-20
0 ImagesSynonyms: H018RAI-20 (H018) is an orally active JAK1/JAK2 dual inhibitor (IC50=15.1 and 22.7 nM). RAI-20 exhibits excellent pharmacokinetic properties, including plasma stability, systemic exposure, and a long half-life. In a collagen-induced arthritis rat model, RAI-20 shows significant anti-inflammatory and anti-arthritic activities, effectively reducing paw swelling volume and arthritis index. RAI-20 can be used for research on the pathogenesis of rheumatoid arthritis.
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YYSW001
0 ImagesCat. No.: HY-182359CAS No.: 2763672-36-0YYSW001 is a selective and orally acrive JAK1 inhibitor with an IC50 of 6 nM and a Kd of 32.32 μM. YYSW001 blocks JAK1-dependent phosphorylation of STAT6, as well as IL-6-induced phosphorylation of STAT3. YYSW001 suppresses pro-inflammatory cytokine levels, reduces paw swelling, lowers clinical arthritis scores, alleviates joint damage and decreases bone loss. YYSW001 is applicable for the research of rheumatoid arthritis.
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Pacritinib hydrochloride
0 ImagesCat. No.: HY-16379ACAS No.: 1228923-43-0Synonyms: SB1518 hydrochloridePacritinib hydrochloride is a potent inhibitor of both wild-type JAK2 (IC50=23 nM) and JAK2V617F mutant (IC50=19 nM). Pacritinib hydrochloride also inhibits FLT3 (IC50=22 nM) and its mutant FLT3D835Y (IC50=6 nM). Pacritinib hydrochloride can be used for the research of acute myeloid leukemia (AML) and myelofibrosis (MF).
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JAK-IN-36
0 ImagesCat. No.: HY-161259JAK-IN-36 (Compound 12e) is a potent and selective inhibitor of Janus Kinase 1 (JAK1) with a IC50 value of 2.2 nM. JAK-IN-36 can be used in the study of autoimmune diseases.
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JAK1-IN-22
0 ImagesCat. No.: HY-187103CAS No.: 2241039-80-3JAK1-IN-22 is a JAK1-selective inhibitor with an IC50 of 1.84 μM. JAK1-IN-22 exerts no significant inhibitory effect on JAK2 and JAK3. JAK1-IN-22 can be used in the research of JAK1-related diseases such as asthma, alopecia areata, and type 1 diabetes.
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JAK-IN-30
0 ImagesCat. No.: HY-154994CAS No.: 2891469-99-9
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JAK1/STAT3-IN-1
0 ImagesCat. No.: HY-170977JAK1/STAT3-IN-1 (compound 4f) is an anti-AD (atopic dermatitis) agent by inhibiting JAK1/STAT3 signaling pathway. JAK1/STAT3-IN-1 inhibits NO generation with an IC50 of 2.17 μM. JAK1/STAT3-IN-1 improves the skin condition of AD-like mice, reduces inflammatory infiltration, inhibits the expressions of p-JAK1/JAK1 and p-STAT3/STAT3, and mitigates the excessive immune response on Calcipotriol (HY-10001) (MC903)-induced AD-like mice.
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JAK1/CDK7-IN-1
0 ImagesCat. No.: HY-181528JAK1/CDK7-IN-1 is a JAK1/CDK7 inhibitor. JAK1/CDK7-IN-1 forms a stable and tightly bound complex with JAK1. JAK1/CDK7-IN-1 disrupts the cell cycle, induces G2/M phase arrest, and increases the proportion of pre-G1 phase cells. JAK1/CDK7-IN-1 induces cellular apoptosis (apoptosis) and necrosis. JAK1/CDK7-IN-1 is applicable to research related to breast cancer and prostate cancer.
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JAK1-IN-20
0 ImagesCat. No.: HY-181872CAS No.: 3106963-85-0JAK1-IN-20 (Compound 38) is a gut-restricted, orally active, selective JAK1 inhibitor with an IC50 of <0.5 nM. JAK1-IN-20 inhibits the enzymatic activity of JAK1, reduces the production of proinflammatory cytokines (TNF-α, IL-6), and suppresses the phosphorylation of STAT3. JAK1-IN-20 ameliorates ulcerative colitis. JAK1-IN-20 can be used for the research of inflammatory bowel disease.
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Momelotinib dihydrochloride
0 ImagesMomelotinib (dihydrochloride) is a JAK1/JAK2 inhibitor that also antagonizes ACVR1, leading to downregulation of Hepcidin expression and increased availability of iron for erythropoiesis. Momelotinib (dihydrochloride) can reduce transfusion burden and spleen enlargement caused by myelofibrosis, showing potential value in research and application within the field of myelofibrosis.
