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]
-
JAK1 Related Products (149)
Related Products (149)
-
Recombinant Proteins (4)
-
Antibodies (2)
-
Tofacitinib-13C,d3
0 ImagesCat. No.: HY-40354S2Synonyms: Tasocitinib-13C,d3; CP-690550-13C,d3Tofacitinib-13C,d3 (Tasocitinib-13C,d3; CP-690550-13C,d3) is the deuterated, 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.
-
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.
-
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.
-
JAK1/2-IN-3
0 ImagesCat. No.: HY-180274JAK1/2-IN-3 is a JAK1 and JAK2 inhibitor with IC50 values of 14.73 nM and 10.03 nM, respectively. JAK1/2-IN-3 induces G2/M cell cycle arrest, and induces intrinsic apoptosis via increased Bax and caspase 3/7 levels and reduced Bcl2 expression. JAK1/2-IN-3 can be used for the study of leukemia cancer, breast cancer and colon cancer.
-
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.
-
JAK1/TYK2-IN-5
0 ImagesCat. No.: HY-175983CAS No.: 3026367-07-4
-
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.
-
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.
-
K882
0 ImagesCat. No.: HY-168893K882 (Compound 4e) is a Src inhibitor, with KD of 0.315 μM. K882 induces Apoptosis. K882 inhibits XIAP and Survivin. K882 inhibits the activation of PI3K/Akt/mTOR, Jak1/Stat3, Ras/MAPK signaling pathways. K882 shows anti-tumor activity against non-small cell lung cancer.
-
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.
-
JAK1-IN-9
0 ImagesCat. No.: HY-144440CAS No.: 2875041-96-4JAK1-IN-9 (compound 23a) is a potent and selective JAK1 inhibitor with an IC50 of 72 nM. JAK1-IN-9 shows selective against other JAKs by 12 times or more.
-
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).
-
Tofacitinib-13C3,15N
0 ImagesCat. No.: HY-40354S1Purity: 99.57%Synonyms: Tasocitinib-13C3,15N; CP-690550-13C3,15NTofacitinib-13C3,15N (Tasocitinib-13C3,15N; CP-690550-13C3,15N) is the 15N, 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.
-
JAK3-IN-18
0 ImagesCat. No.: HY-174999CAS No.: 2914873-59-7JAK3-IN-18 is an orally active JAK3 and TEC inhibitor, with IC50s of 0.5391 nM and 12.40 nM, respectively. JAK3-IN-18 demonstrates outstanding selectivity over AK1, AK2, and TYk2, with selectivity ratios exceeding 10,000-fold. JAK3-IN-18 demonstrates excellent therapeutic efficacy in the experimental autoimmune encephalomyelitis (EAE) mouse model. JAK3-IN-18 can be used for the study of multiple sclerosis.
-
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.
