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Recent developments on JAK2 inhibitors: a patent review

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Pages 471-495 | Published online: 08 Mar 2010

Bibliography

  • Leonard WJ, O'Shea JJ. Jaks and STATs: biological implications. Annu Rev Immunol 1998;16:293-322
  • Ward AC, Touw I, Yoshimura A. The Jak-Stat pathway in normal and perturbed hematopoiesis. Blood 2000;95:19-29
  • Verma A, Kambhampati S, Parmar S, Platanias LC. Jak family of kinases in cancer. Cancer Metastasis Rev 2003;22:423-34
  • Levine RL, Belisle C, Wadleigh M, X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. Blood 2006;107:4139-41
  • Baxter EJ, Scott LM, Campbell PJ, Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61
  • Kralovics R, Passamonti F, Buser AS, A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-90
  • Kumar C, Purandare AV, Lee FY, Lorenzi MV. Kinase drug discovery approaches in chronic myeloproliferative disorders. Oncogene 2009;28:2305-13
  • Sayyah J, Sayeski PP. Jak2 inhibitors: rationale and role as therapeutic agents in hematologic malignancies. Curr Oncol Rep 2009;11:117-24
  • Apostolidou E, Kantarjian HM, Verstovsek S. JAK2 inhibitors: a reality? A hope? Clin Lymphoma Myeloma 2009;9(Suppl 3):S340-5
  • Barosi G, Rosti V. Novel strategies for patients with chronic myeloproliferative disorders. Curr Opin Hematol 2009;16:129-34
  • Wilks AF. The JAK kinases: not just another kinase drug discovery target. Semin Cell Dev Biol 2008;19:319-28
  • Atallah E, Verstovsek S. Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms. Expert Rev Anticancer Ther 2009;9:663-70
  • Pardanani A. JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials. Leukemia 2008;22:23-30
  • Pesu M, Laurence A, Kishore N, Therapeutic targeting of Janus kinases. Immunol Rev 2008;223:132-42
  • Meydan N, Grunberger T, Dadi H, Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature 1996;379:645-8
  • Luo C, Laaja P. Inhibitors of JAKs/STATs and the kinases: a possible new cluster of drugs. Drug Discov Today 2004;9:268-75
  • Ugo V, Marzac C, Teyssandier I, Multiple signalling pathways are involved in erythropoietin-independent differentiation of erythroid progenitors in polycythemia vera. Exp Hematol 2004;32:179-87
  • Faderl S, Harris D, Van Q, Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces antiapoptotic and proapoptotic signals in acute myeloid leukemia. Blood 2003;102:630-7
  • University of Texas System. Compounds for treatment of cell proliferative diseases. WO05058829; 2005
  • Verstovsek S, Manshouri T, Quintás-Cardama A, WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res 2008;14:788-96
  • Ferrajoli A, Faderl S, Van Q, WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res 2007;67:11291-9
  • Hospital for Sick Children (HSC) Research and Development Limited Partnership. Novel compounds for modulating cell proliferation. WO01079158; 2001
  • Lipka DB, Hoffmann LS, Heidel F, LS104, a non-ATP-competitive small-molecule inhibitor of JAK2, is potently inducing apoptosis in JAK2V617F-positive cells. Mol Cancer Ther 2008;7:1176-84
  • Hospital for Sick Children (HSC) Research and Development Limited Partnership. Styryl acrylonitrile compounds and their use to promote myelopoiesis. WO03030895; 2003
  • Hospital for Sick Children (HSC) Research and Development Limited Partnership. Inhibition of vascular endothelial growth factor. WO04032911; 2004
  • Hospital for Sick Children (HSC) Research and Development Limited Partnership. Novel compounds for modulating cell proliferation. WO05092904; 2005
  • Brigham & Women's Hospital, Inc. Kinase inhibitors and methods of use thereof. WO03068157; 2003
  • Mor-Research Applications Ltd, Yissum Research Development Co. of the Hebrew University of Jerusalem. Pharmaceutical compositions comprising tyrphostins. WO98006391; 1998
  • Jatiani SS, Cosenza SC, Pallela VR, Identification of a dual JAK2/BCR-ABL kinase inhibitor for treatment of myeloproliferative disorders. AACR Annual Meeting (Meeting Abstracts); 18 – 22 April 2009; Denver, CO, USA
  • Thompson JE, Cubbon RM, Cummings RT, Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor. Bioorg Med Chem Lett 2002;12:1219-23
  • Lucet IS, Fantino E, Styles M, The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood 2006;107:176-83
  • Merck & Co., Inc. Benzimidazo[4,5-f]isoquinolinone derivatives. WO03011285; 2003
  • Pedranzini L, Dechow T, Berisha M, Pyridone 6, A pan-Janus-activated kinase inhibitor, induces growth inhibition of multiple myeloma cells. Cancer Res 2006;66:9714-21
  • Kwak HB, Kim HS, Lee MS, Pyridone 6, a pan-Janus-activated kinase inhibitor, suppresses osteoclast formation and bone resorption through down-regulation of receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced c-Fos and nuclear factor of activated T cells (NFAT) c1 expression. Biol Pharm Bull 2009;32:45-50
  • University of Texas System. Suppression of STAT3 reactivation after Src kinase inhibition to treat cancer. WO08077062; 2008
  • Mathur A, Moa JR, Kraus M, An inhibitor of Janus kinase 2 prevents polycythemia in mice. Biochem Pharmacol 2009;78:382-9
  • Merck & Co., Inc. Inhibitors of Janus kinases. WO09035575; 2009
  • Vertex Pharmaceuticals, Inc. Processes for preparing substituted pyrimidines and pyrimidine derivatives as inhibitors of protein kinase. WO04000833; 2004
  • Vertex Pharmaceuticals, Inc. AbI kinase inhibition. WO07014250; 2007
  • Merck & Co., Inc. RET tyrosine kinase inhibition. WO07087245; 2007
  • Harrington EA, Bebbington D, Moore J, VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 2004;10:262-7
  • Merck & Co., Inc., Vertex Pharmaceuticals, Inc. JAK2 tyrosine kinase inhibition. WO07087246; 2007
  • Ambit Biosciences Corp. Methods of treating certain diseases using pyrimidine derivatives. WO09073224; 2009
  • Available from: www.drugresearcher.com/Emerging-targets/Merck- Vertex-halt-aurora-kinase-cancer-trial. [Last accessed 13 January 2010]
  • Vertex Pharmaceuticals, Inc. Aminopyrimidines useful as kinase inhibitors. WO07056164; 2007
  • Vertex Pharmaceuticals, Inc. Aminopyrimidines useful as kinase inhibitors. WO07056163; 2007
  • Vertex Pharmaceuticals, Inc. Diaminotriazole compounds useful as protein kinase inhibitors. WO06034116; 2006
  • Wang T, Duffy JP, Wang J, Janus kinase 2 inhibitors. Synthesis and characterization of a novel polycyclic azaindole. J Med Chem 2009;52(24):7938-42
  • Vertex Pharmaceuticals, Inc. Deazapurines useful as inhibitors of Janus kinases. WO07041130; 2007
  • Vertex Pharmaceuticals, Inc. Deazapurines useful as inhibitors of Janus kinases. WO07117494; 2007
  • Vertex Pharmaceuticals, Inc. Azaindoles useful as inhibitors of Janus kinases. WO07084557; 2007
  • Vertex Pharmaceuticals, Inc. Tricyclic heteroaryl compounds useful as inhibitors of Janus kinase. WO08079521; 2008
  • Ledeboer MW, Pierce AC, Duffy JP, 2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2. Bioorg Med Chem Lett 2009;19:6529-33
  • Vertex Pharmaceuticals, Inc. Pyrazolo[1,5-a]pyrimidines useful as JAK2 inhibitors. WO09085913; 2009
  • Cytopia Research Pty Ltd. Kinase inhibitors. WO03099811; 2003
  • Cytopia Research Pty Ltd. Phenyl amino pyrimidine compounds and uses thereof. WO08109943; 2008
  • Pardanani A, Lasho T, Smith G, CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia 2009;23:1441-5
  • Cytopia Research Pty Ltd. Retrometabolic compounds. WO09029998; 2009
  • TargeGen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases. WO07053452; 2007
  • Pardanani A, Hood J, Lasho T, TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia 2007;21:1658-68
  • Wernig G, Kharas MG, Okabe R, Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell 2008;13:311-20
  • Geron I, Abrahamsson AE, Barroga CF, Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. Cancer Cell 2008;13:321-30
  • TargeGen, Inc. Anilinopyrimidines as JAK kinase inhibitors. WO09046416; 2009
  • AstraZeneca AB. Pyrazolylaminopyridine derivatives useful as kinase inhibitors. WO06082392; 2006
  • AstraZeneca AB. Pyrazolyl derivatives with analgesic activity and therefore useful in the treatment or prophylaxis of pain. WO08054292; 2008
  • Gozgit JM, Bebernitz G, Patil P, Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2. J Biol Chem 2008;283:32334-43
  • Ioannidis S, Lamb ML, Davies AM, Discovery of pyrazol-3-ylamino pyrazines as novel JAK2 inhibitors. Bioorg Med. Chem Lett 2009;19:6524-8
  • AstraZeneca AB. Pyrazolyl-amino-substituted pyrazines and their use for the treatment of cancer. WO08117050; 2008
  • AstraZeneca AB. 4-(3-Aminopyrazole)pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer. WO07049041; 2007
  • AstraZeneca AB. Chemical compounds. WO09095712; 2009
  • AstraZeneca AB. Amino-thiazolyl-pyrimidine derivatives and their use for the treatment of cancer. WO08135786; 2008
  • AstraZeneca AB. Pyrazolyl-amino-substituted pyrimidines and their use for the treatment of cancer. WO08132502; 2008
  • AstraZeneca AB. Chemical compounds 000-1. WO09027736; 2009
  • AstraZeneca AB. Chemical compounds 916-1. WO09007753; 2009
  • AstraZeneca AB. 5-Aminopyrazol-3-yl-3H-imidazo[4,5-b]pyridine derivatives and their use for the treatment of cancer. WO08129255; 2008
  • AstraZeneca AB. 9-(Pyrazol-3-yl)-9H-purine-2-amine and 3-(pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine derivatives and their use for the treatment of cancer. WO08135785; 2008
  • Novartis AG. Combinations of JAK inhibitors. WO06056399; 2006
  • Novartis AG. Sulphonamidoaniline derivatives being Janus kinases inhibitors. WO07071393; 2007
  • Novartis AG. 2,4-Di(arylamino)-pyrimidine-5-carboxamide compounds as JAK kinases inhibitors. WO08009458; 2008
  • Novartis AG. Heterocyclic compounds as antiinflammatory agents. WO08052734; 2008
  • Novartis AG. Quinoxaline derivatives as inhibitors of the tyrosine kinase activity of Janus kinases. WO08148867; 2008
  • Novartis AG. Pyrrolo[2,3-d]pyridines and use thereof as tyrosine kinase inhibitors. WO09098236; 2009
  • Exelixis, Inc. 4-Aryl-2-amino-pyrimidines or 4-aryl-2-aminoalkyl-pyrimidines as JAK-2 modulators and methods of use. WO07089768; 2007
  • Exelixis, Inc. JAK-2 modulators and methods of use. WO08042282; 2008
  • S*BIO Pte Ltd. Oxygen linked pyrimidine derivatives. WO07058627; 2007
  • S*BIO Pte Ltd. Heteroalkyl linked pyrimidine derivatives. WO07058628; 2007
  • S*BIO Pte Ltd. Indole sustituted pyrimidines and use thereof in the treatment of cancer. WO08060248; 2008
  • S*BIO Pte Ltd. Pyridyl substituted pyrimidine derivatives. WO08140419; 2008
  • S*BIO Pte Ltd. Pyrimidine derivatives. WO08140420; 2008
  • S*BIO Pte Ltd. Heterocycloalkyl substiituted pyrimidine derivatives. WO08140421; 2008
  • Sgx Pharmaceuticals, Inc. Pyrimidinyl-thiophene kinase modulators. WO07053776; 2007
  • Antonysamy S, Hirst G, Park F, Fragment-based discovery of JAK-2 inhibitors. Bioorg Med Chem Lett 2009;19:279-82
  • Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway. WO08118822; 2008
  • Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway. WO08118823; 2008
  • Rigel Pharmaceuticals, Inc. Pyrimidine-2-amine compounds and their use as inhibitors of JAK kinases. WO09103032; 2009
  • SuperGen, Inc. Pyrimidine-2,4-diamine derivatives and their use as JAK2 kinase inhibitors. WO08106635; 2008
  • ChemBridge Research Laboratories, Inc. Tricyclic compound derivatives useful in the treatment of neoplastic diseases, inflammatory disorders and immunomodulatory disorders. WO08021369; 2008
  • Kyowa Hakko Kirin Co., Ltd. JAK inhibitor. EP2108642; 2009
  • Abbott Laboratories, Inc. 5-Heteroaryl substituted indazoles as kinase inhibitors. WO08154241; 2008
  • Incyte Corp. Azetidine and cyclobutane derivatives as JAK inhibitors. WO09114512; 2009
  • Incyte Corp. Metabolites of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-lH- pyrazol-l-yl)-3-cyclopentylpropanenitrile. WO08157207; 2008
  • Phenomix Corp. Inhibitors of JAK2 kinase. WO09017954; 2009
  • F. Hoffmann-La Roche AG. Pyrrolopyrazine kinase inhibitors. WO09106441; 2009
  • F. Hoffmann-La Roche AG. Pyrrolopyrazine kinase inhibitors. WO09106443; 2009
  • Kyowa Hakko Kirin Co., Ltd. Derivatives of physiologically active substance K-252. WO88007045; 1988
  • Levis M, Tse KF, Smith BD, A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harbouring FLT3 internal tandem duplication mutations. Blood 2001;98:885-7
  • Cephalon, Inc. JAK inhibitors for treatment of myeloproliferative disorders. WO08011174; 2008
  • Hexner EO, Serdikoff C, Jan M, Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 2008;111:5663-71
  • Muto A, Hori M, Sasaki Y, Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor. Mol Cancer Ther 2007;6:987-94
  • Duan Z, Bradner J, Greenberg E, 8-Benzyl-4-oxo-8-azabicyclo[3.2.1]oct-2-ene-6,7-dicarboxylic Acid (SD-1008), a novel Janus kinase 2 inhibitor, increases chemotherapy sensitivity in human ovarian cancer cells. Mol Pharmacol 2007;72:1137-45
  • Flowers LO, Johnson HM, Mujtaba MG, Characterization of a peptide inhibitor of Janus kinase 2 that mimics suppressor of cytokine signaling 1 function. J Immunol 2004;172:7510-8
  • University of South Florida (USF). Materials and methods for treatment of cancer and identification of anti-cancer compounds. WO02078617; 2002
  • Sandberg EM, Ma X, He K, Identification of 1,2,3,4,5,6-hexabromocyclohexane as a small molecule inhibitor of Jak2 tyrosine kinase autophophorylation. J Med Chem 2005;48:2526-33
  • Sayyah J, Magis A, Ostrov DA, Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth. Mol Cancer Ther 2008;7:2308-18
  • Kiss R, Polgár T, Kirabo A, Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening. Bioorg Med Chem Lett 2009;19:3598-601
  • University of South Florida (USF). Combination therapies for cancer and proliferative angiopathies. WO05110477; 2005
  • Oregon Health and Science University (OHSU). Methods for treating induced cellular proliferative disorders. WO09073575; 2009
  • Parganas E, Wang D, Stravopodis D, Jak2 is essential for signaling through a variety of cytokine receptors. Cell 1998;93:385-95
  • Neubauer H, Cumano A, Muller M, Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 1998;93:397-409

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