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Janus Reveals Another Face: The Biologic Rationale for Targeting Janus Kinase 2 in Lymphoma
Journal of Clinical Oncology, 2012The Janus kinases (JAKs), nonreceptor protein tyrosine kinases that mediate cytokine receptor signaling, are important drivers of multiple hematologic malignancies. Canonical JAK–signal transducer and activator of transcription (STAT) signaling results in phosphorylation of STAT transcription factors, which translocate to the nucleus, bind DNA, and ...
Ann, Mullally, Benjamin L, Ebert
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Prolactin Promotes Hepatocellular Carcinoma through Janus Kinase 2
World Journal of Surgery, 2012AbstractBackgroundHepatocelluar carcinoma (HCC) is one human cancer with obvious gender disparity. This study investigated the association of aberrant prolactin levels with HCC risk and the potential impacts on HCC of the prolactin receptor (PRLR)/Janus kinase 2 (JAK2) signaling.MethodsSerum prolactin of 63 HCC patients and 162 subjects without HCC was
Yao-Tsung, Yeh +4 more
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Discovery of Potent and Selective Pyrazolopyrimidine Janus Kinase 2 Inhibitors
Journal of Medicinal Chemistry, 2012The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in discovering selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibitor of Jak2.
Emily J, Hanan +22 more
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Janus kinase 2 is involved in lipopolysaccharide-induced activation of macrophages
American Journal of Physiology-Cell Physiology, 2003The mechanisms by which lipopolysaccharide (LPS) is recognized, and how such recognition leads to innate immune responses, are poorly understood. Stimulation with LPS induces the activation of a variety of proteins, including mitogen-activated protein kinases (MAPKs) and NF-κB.
Shu, Okugawa +7 more
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Janus kinase-2 signaling mediates apoptosis in rat cardiomyocytes
Vascular Pharmacology, 2005We tested the hypothesis that activation Jak2, which is prominently involved in the up-regulation of the renin-angiotensin system (RAS), constitutes a focal point in relaying signals triggered by a Angiotensin II (Ang II) and hypoxia/reoxygenation separately to cause an enhanced susceptibility of cardiac myocyte to apoptotic cell death.
Eduardo, Mascareno +2 more
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Modulation of Janus kinase 2 by p53 in ovarian cancer cells
Biochemical and Biophysical Research Communications, 2004The constitutive activation of the Janus kinase 2 (JAK2) and mutation of the p53 tumor suppressor are both detected in human cancer. We examined the potential regulation of JAK2 phosphorylation by wild-type (wt) p53 in human ovarian cancer cell lines, Caov-3 and MDAH2774, which harbor mutant form of p53 tumor suppressor gene and high levels of ...
Thomas, Reid +5 more
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Specific dephosphorylation of Janus Kinase 2 by protein tyrosine phosphatases
PROTEOMICS, 2014Many protein kinases are activated through phosphorylation of an activation loop thereby turning on downstream signaling pathways. Activation of JAK2, a nonreceptor tyrosine kinase with an important role in growth factor and cytokine signaling, requires phosphorylation of the 1007 and 1008 tyrosyl residues.
Jianzhuo, Li +9 more
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Downregulation of Chloride Channel ClC-2 by Janus Kinase 3
The Journal of Membrane Biology, 2014Janus kinase-3 (JAK3) fosters proliferation and counteracts apoptosis of lymphocytes and tumor cells. The gain of function mutation (A572V)JAK3 has been discovered in acute megakaryoplastic leukemia. JAK3 is inactivated by replacement of lysine by alanine in the catalytic subunit ((K855A)JAK3).
Jamshed, Warsi +4 more
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Inhibition of Janus kinase 2 by cyclometalated rhodium complexes
MedChemComm, 2012Cyclometalated rhodium complexes were synthesized and evaluated as JAK2 metal-based inhibitors. Complexes 1 and 2 inhibited JAK2 enzyme phosphorylation activity, reduced JAK2 autophosphorylation in cellulo and exhibited cytotoxicity towards HEL cancer cells. To our knowledge, these are the first two examples of metal-based inhibitors of JAK2.
Chung-Hang Leung +7 more
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Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors
Bioorganic & Medicinal Chemistry, 2017Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized.
Yazhou, Wang +8 more
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