JAK2
JAK2 is a non-receptor tyrosine kinase in the JAK1-JAK2-JAK3-TYK2 family and acts as a cytoplasmic signaling component of cytokine receptors[1]. Mechanistically, cytokine-mediated activation of JAK2 promotes receptor phosphorylation, recruits STAT proteins, and drives STAT phosphorylation-dependent transcriptional signaling[1][2]. This pathway supports cell growth, survival, development, differentiation, hematopoiesis, immune regulation, and homeostasis[2][3]. In disease models, gain-of-function JAK2 V617F in the pseudokinase domain causes constitutive activity and is strongly linked to myeloproliferative neoplasms and leukemias[1][4]. Compared with related isoforms, JAK3 is essential for common γ-chain cytokine receptor signaling in T- and B-cell development, whereas complete mouse deletion of JAK1 or JAK2 is not compatible with life[5][6]. For experimental applications, ruxolitinib is a selective oral JAK1/JAK2 inhibitor, and JAK2-focused compounds support studies of mutant signaling, cytokine responses, splenomegaly, angiogenesis, and inhibitor resistance[7][8][9].
References:
- [1]. Hubbard SR. Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase. Front Endocrinol (Lausanne). 2018 Jan 5;8:361. doi: 10.3389/fendo.2017.00361. PMID: 29379470; PMCID: PMC5770812. et al. Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase. Front Endocrinol (Lausanne). 2018 Jan 5;8:361. [Content Brief]
- [2]. Ihle JN, et al. Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet. 1995 Feb;11(2):69-74. [Content Brief]
- [3]. Rawlings JS, et al. The JAK/STAT signaling pathway. J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3. [Content Brief]
- [4]. Gäbler K, et al. JAK2 mutants (e.g., JAK2V617F) and their importance as drug targets in myeloproliferative neoplasms. JAKSTAT. 2013 Jul 1;2(3):e25025. [Content Brief]
- [5]. Suzuki K, et al. Janus kinase 3 (Jak3) is essential for common cytokine receptor gamma chain (gamma(c))-dependent signaling: comparative analysis of gamma(c), Jak3, and gamma(c) and Jak3 double-deficient mice. Int Immunol. 2000 Feb;12(2):123-32. [Content Brief]
- [6]. Ghoreschi K, et al. Janus kinases in immune cell signaling. Immunol Rev. 2009 Mar;228(1):273-87. [Content Brief]
- [7]. Naqvi K, et al. A potential role of ruxolitinib in leukemia. Expert Opin Investig Drugs. 2011 Aug;20(8):1159-66. [Content Brief]
- [8]. Hart S, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia. 2011 Nov;25(11):1751-9. [Content Brief]
- [9]. Cheng Z, et al. Angiogenesis in JAK2 V617F positive myeloproliferative neoplasms and ruxolitinib decrease VEGF, HIF-1 enesis in JAK2 V617F positive cells. Leuk Lymphoma. 2018 Jan;59(1):196-203. [Content Brief]
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JAK2 Related Products (209)
Related Products (209)
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Antibodies (3)
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Itacnosertib hydrochloride
0 ImagesSynonyms: TP-0184 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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SJ1008030 formic
0 ImagesCat. No.: HY-147330BPurity: 98.91%
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JAK1-IN-8
0 ImagesCat. No.: HY-139423CAS No.: 1973485-18-5JAK1-IN-8, a potent JAK1 inhibitor (IC50<500 nM), compound 28, extracted from patent WO2016119700A1.
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PROTAC JAK1/2 degrader-1
0 ImagesCat. No.: HY-179715Purity: 99.47%PROTAC JAK1/2 degrader-1 is an orally active JAK1/JAK2 PROTAC degrader, with DC50 values of 1.4 μM and 0.92 μM against JAK1 and JAK2, respectively. PROTAC JAK1/2 degrader-1 triggers degradation via a CRBN- and proteasome-dependent pathway. PROTAC JAK1/2 degrader-1 inhibits the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). PROTAC JAK1/2 degrader-1 alleviates inflammatory responses and colon injury by inhibiting the JAK/STAT3 signaling pathway. PROTAC JAK1/2 degrader-1 can be used for the research of inflammatory bowel disease.
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GSK2646264
0 ImagesGSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.1. GSK2646264 also inhibits other kinases with pIC50 values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin.
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Ilginatinib maleate
0 ImagesSynonyms: NS-018 maleate
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Flonoltinib TFA
0 ImagesSynonyms: JAK2/FLT3-IN-1 TFA
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Phlorizin dihydrate
0 ImagesPhlorizin (Floridzin) dihydrate is an orally active non-selective sodium-glucose cotransporter (SGLT) inhibitor, with an IC50 of 0.04 μM and a Ki of 39 nM against hSGLT2, and an IC50 of 0.17 μM and a Ki of 0.31 μM against hSGLT1. Phlorizin dihydrate promotes GLUT4 translocation, inhibits gluconeogenesis and promotes glycogen synthesis by activating the PI3K/Akt/mTOR pathway. Phlorizin dihydrate reduces DNA damage and apoptosis (apoptosis) by inhibiting the NF-κB inflammatory pathway. Phlorizin dihydrate induces apoptosis via activating the Caspase pathway by antagonizing the JAK/STAT3 and PCK pathways. Phlorizin dihydrate also exhibits antibacterial, anti-inflammatory and neuroprotective activities.
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M351-0056
0 ImagesM351-0056 is an orally active VISTA agonist with a Kd value of 12.60 μM. M351-0056 inhibits the activation of the JAK2-STAT2 pathway, reduces the phosphorylation levels of JAK2 and STAT2, and regulates type I interferon (IFN-I) and non-canonical NF-κB pathways. M351-0056 decreases the levels of cytokines (IFN-γ, IL-17A, TNF-α, IL-2 and IL-1β). M351-0056 improves imiquimod (HY-B0180)-induced psoriasis-like skin inflammation, reduces autoantibody levels, kidney damage and immune cell expansion in mice susceptible to chronic graft-versus-host disease and lupus, and delays the progression of systemic lupus erythematosus. M351-0056 can be used in research related to psoriasis-like dermatitis and systemic lupus erythematosus.
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ZT55
0 ImagesZT55 is an orally active and highly-selective JAK2 inhibitor with an IC50 value of 0.031 μM. ZT55 inhibits the proliferation of JAK2V617F-expressing HEL cell lines and induces apoptosis and cycle arrest. ZT-55 also effectively inhibits the growth of HEL xenograft tumours in a mice model. ZT-55 can be used in studies of myeloproliferative neoplasms, polycythemia vera and primary thrombocythemia.
