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]
-
JAK2 Related Products (205)
Related Products (205)
-
Antibodies (3)
-
Fedratinib hydrochloride hydrate
0 ImagesSynonyms: TG-101348 hydrochloride hydrate; SAR 302503 hydrochloride hydrateFedratinib hydrochloride hydrate (TG-101348 hydrochloride hydrate) is a potent, selective, ATP-competitive and orally active JAK2 inhibitor with IC50s of 3 nM for both JAK2 and JAK2V617F kinase. Fedratinib hydrochloride hydrate shows 35- and 334-fold selectivity over JAK1 and JAK3, respectively. Fedratinib hydrochloride hydrate induces cancer cell apoptosis and has the potential for myeloproliferative disorders research.
-
Oclacitinib
0 ImagesSynonyms: PF-03394197
-
Lestaurtinib
0 ImagesSynonyms: CEP-701; KT-5555Lestaurtinib (CEP-701) is an orally active and selective RPTKs (receptor protein tyrosine kinase) inhibitor, competitively inhibits ATP binding to the TrkA/B/C domain. Lestaurtinib inhibits RPTKs phosphorylation, with IC50s of 2, 25 and 0.9 nM for FLT3, TrkA and JAK2, respectively. Lestaurtinib induces apoptosis and cycle arrest, also can inhibit growth of tumor.
-
NSC 42834
0 ImagesCat. No.: HY-15480CAS No.: 195371-52-9Synonyms: JAK2 Inhibitor V; Z3NSC 42834 (JAK2 Inhibitor V), a novel specific inhibitor of Jak2, inhibits Jak2-V617F and Jak2-WT autophosphorylation in a dose-dependent manner but was not cytotoxic to cells at concentrations that inhibited kinase activity.
-
(E/Z)-Zotiraciclib
0 ImagesSynonyms: (E/Z)-TG02; (E/Z)-SB1317
-
RGB-286638
0 ImagesRGB-286638 is a potent inhibitor of CDK and MAPK9. RGB-286638 inhibits the activities of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3 and p35-CDK5, with IC50 values of 1, 2, 3, 4, 5 and 5 nM, respectively. RGB-286638 inhibits GSK-3β and TAK1, with IC50 values of 3 nM and 5 nM, respectively. RGB-286638 induces caspase-dependent Apoptosis in cells. RGB-286638 delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 extends survival in multiple myeloma models. RGB-286638 can be used in research related to glioblastoma and multiple myeloma.
-
Oclacitinib monomaleate
0 ImagesSynonyms: PF-03394197 monomaleate
-
Radotinib
0 ImagesSynonyms: IY-5511Radotinib (IY-5511) is an orally active and BBB-permeable selective tyrosine kinase Bcr-Abl1 inhibitor with an IC50 of 34 nM. Radotinib has anti-prion and anti-tumor activities. Radotinib can inhibit the proliferation, induce cell cycle arrest and apoptosis of tumor cells . Radotinib can be used in the research of cancer such as chronic myeloid leukemia and multiple myeloma, as well as neurodegenerative diseases such as prion diseases.
-
SJ10542
0 ImagesSJ10542 is a potent and selective JAK2/3 PROTAC degrader, with DC50 values of 14 nM and 11 nM against JAK2 and JAK3, respectively. SJ10542 exhibits anti-tumor activity and can be used for research on acute lymphoblastic leukemia.
-
Atinvicitinib
0 ImagesAtinvicitinib is an orally active and selective JAK1 inhibitor. Atinvicitinib blocks signaling of JAK1-dependent pruritogenic and pro-inflammatory cytokines, including those in the IL-31, IL-4, and IL-13 pathways. Atinvicitinib can be used for the researches of pruritus associated with allergic dermatitis and canine atopic dermatitis.
