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 (150)
Related Products (150)
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Recombinant Proteins (4)
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Antibodies (2)
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JNK-IN-17
0 ImagesCat. No.: HY-164111CAS No.: 1128096-58-1JNK-IN-17 (Compound 9J) is a selective and potent JNK inhibitor with IC50 values of 0.039, 0.079 μM for JNK1 and JNK3. JNK-IN-17 can inhibit c-Jun phosphorylation with an IC50 of 0.082 μM in Streptozotocin (HY-13753)-infuced INS-1 pancreatic islet β cells. JNK-IN-17 shows inhibition rate ≤ 33% on the four main P450 subtypes (2C9, 2D6, 3A4, 1A2) in human liver microsomes, indicating a relatively low risk of drug interactions. JNK-IN-17 can be used for researches of neurological and metabolic disease, such as Parkinson's disease.
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(R)-Blovacitinib
0 ImagesCat. No.: HY-152080ACAS No.: 2411222-96-1Synonyms: (R)-TUL01101(R)-Blovacitinib ((R)-TUL01101) is a JAK1-selective inhibitor with an IC50 of 45 nM. (R)-Blovacitinib inhibits JAK1-mediated cytokine signaling pathways. (R)-Blovacitinib can be used for the research of rheumatoid arthritis.
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JAK1-IN-21
0 ImagesCat. No.: HY-184592JAK1-IN-21, biotin-conjugated isoxazole derivative, is a JAK1 inhibitor. JAK1-IN-21 directly engages and stabilizes JAK1, reduces the phosphorylation of JAK1, STAT1 and AKT, induces apoptotic marker cleavage (PARP, Caspase-3, Caspase-7) and exhibits broad-spectrum antiproliferative activity against cancer cells. JAK1-IN-21 can be used for the study of liver cancer, prostate cancer, and breast cancer.
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JAK/HDAC-IN-2
0 ImagesCat. No.: HY-149283CAS No.: 3029138-43-7JAK/HDAC-IN-2 is a potent 2-amino-4-phenylaminopyrimidine JAK/HDAC dual-target inhibitor. JAK/HDAC-IN-2 potently inhibits HDAC3/6 and JAK1/2 at nanomolar levels. JAK/HDAC-IN-2 has proapoptotic activity and inhibits histone deacetylation and STAT3 phosphorylation. JAK/HDAC-IN-2 presents remarkable antiproliferative activity in both hematological malignancies and solid cancers.
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JAK3/BTK-IN-6
0 ImagesCat. No.: HY-147754CAS No.: 2243136-03-8
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JAK1-IN-10
0 ImagesCat. No.: HY-153566CAS No.: 2416858-88-1JAK1-IN-10 (compound 9), a cyano-substituted cyclic hydrazine derivative, is a potent and selective JAK1 inhibitor.
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MRC-G-001
0 ImagesCat. No.: HY-175009MRC-G-001 is a Genipin (HY-17389) derivative with an IC50 of 117 μM against A549 cancer cells. MRC-G-001 inhibits the phosphorylation of EGFR, JAK1, and STAT3, and modulates epithelial-mesenchymal transition (EMT)-related protein expression, thereby attenuating cell migration and invasion. MRC-G-001 induces cell cycle arrest and cell apoptosis. MRC-G-001 can be used for the study of cancers such as non-small-cell lung cancer.
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JAK2-IN-14
0 ImagesCat. No.: HY-175684CAS No.: 3087335-24-5JAK2-IN-14 is an orally active JAK2 inhibitor with an IC50 of 2 nM. JAK2-IN-14 demonstrates 89.5-, 80.5-, and 51-fold selectivity over JAK1, JAK3, and TYK2, respectively. JAK2-IN-14 inhibits STAT5 signaling pathway. JAK2-IN-14 causes tumor cell cycle arrest and apoptosis. JAK2-IN-14 can used for the study of myeloproliferative neoplasms (MPNs).
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oJak-989
0 ImagesCat. No.: HY-W635076CAS No.: 1315485-91-6
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LAS194046
0 ImagesCat. No.: HY-150101CAS No.: 1798578-61-6LAS194046 is a selective pan-JAK inhibitor, with an IC50 of 5.46 nM against JAK1, 0.4 nM against JAK2, and 2.07 nM against JAK3. LAS194046 reduces the levels of IL-8 and MMP-9. LAS194046 enhances the activation of glucocorticoid response elements by Fluticasone propionate. LAS194046 inhibits T2-type allergic pulmonary inflammation, allergen-induced airway inflammation, and late-phase asthmatic responses in rats. LAS194046 can be used in research related to non-T2 severe asthma, chronic obstructive pulmonary disease, and asthma.
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JAK3-IN-12
0 ImagesCat. No.: HY-147975CAS No.: 1430095-86-5JAK3-IN-12 (compound 5k) is a highly potent JAK3 inhibitor with IC50 values of 9.5 nM, 18 nM and 42 nM for JAK3, JAK1 and JAK2, respectively. JAK3-IN-12 can be used for researching rheumatoid arthritis.
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Jak1 RIMTAC-1
0 ImagesCat. No.: HY-187502Jak1 RIMTAC-1 is a JAK1 RIMTAC degrader (a PROTAC-like agent) with a DC50 of 322.8 nM. Jak1 RIMTAC-1 forms a ternary complex with JAK1 and RIPK1, thereby recruiting the VHL E3 ligase complex to ubiquitinate JAK1 via the ubiquitin-proteasome system and mediate its subsequent proteasomal degradation. Jak1 RIMTAC-1 does not alter JAK1 mRNA levels (pink: Jak1 ligand-1 (HY-187503); blue: RIPK1-ligand-4 (HY-187391); black: Linker (HY-B0704)).
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JAK1-IN-19
0 ImagesCat. No.: HY-178282CAS No.: 2169271-17-2
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JAK1/2-IN-2
0 ImagesCat. No.: HY-177006CAS No.: 1470249-04-7JAK1/2-IN-2 (Compound 37) is a potent and selective JAK1/2 inhibitor with Ki values of 2 and 0.6 nM .
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JAK-IN-44
0 ImagesCat. No.: HY-188034CAS No.: 2119040-02-5JAK-IN-44 is an orally active and selective JAK2 inhibitor, with IC50 values of 0.2 nM, 7.3 nM, 21 nM and 27 nM against JAK2, TYK2, JAK1 and JAK3, respectively. JAK-IN-44 inhibits disease phenotypes in adjuvant-induced arthritis, systemic lupus erythematosus and experimental autoimmune uveitis models, and improves the survival rate of mice in LPS (HY-D1056)-induced sepsis models. JAK-IN-44 can be used in the research of autoimmune and inflammatory diseases such as systemic lupus erythematosus, uveitis, rheumatoid arthritis and sepsis.
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JAK-IN-38
0 ImagesCat. No.: HY-162862JAK-IN-38 (Compound 1) is a JAK inhibitor, with IC50s of 0.03, 0.06, 0.12, 0.44 μM for Tyk2, JAK3, JAK2, JAK1 respectively. JAK-IN-38 is a collagen VII (C7) inducer and has anti-inflammatory activity. JAK-IN-38 can upregulate the expression of COL7A1 mRNA in donor-derived keratinocytes and works together with Gentamicin (HY-A0276A) to boost overall C7 levels.
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Tofacitinib hydrochloride
0 ImagesCat. No.: HY-40354HCAS No.: 1803005-18-6Synonyms: Tasocitinib hydrochloride; CP-690550 hydrochlorideTofacitinib hydrochloride (Tasocitinib hydrochloride) is an orally active, blood-brain barrier permeable selective inhibitor of JAK1/JAK3. Tofacitinib hydrochloride blocks the JAK-STAT/NF-κB signaling pathway, inhibits cytokine signal transduction, phosphorylation of STAT1/STAT5, and suppresses innate and adaptive immune responses. Tofacitinib hydrochloride 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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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.
