User menu

Rethinking JAK2 Inhibition: Towards Novel Strategies of More Specific and Versatile Janus Kinase Inhibition

Bibliographic reference Leroy, Emilie ; Constantinescu, Stefan N.. Rethinking JAK2 Inhibition: Towards Novel Strategies of More Specific and Versatile Janus Kinase Inhibition. In: Leukemia,
Permanent URL http://hdl.handle.net/2078.1/181521
  1. Vainchenker W, Constantinescu S N, JAK/STAT signaling in hematological malignancies, 10.1038/onc.2012.347
  2. Briscoe J, EMBO J, 15, 799 (1996)
  3. Drachman Jonathan G., Millett Kelly M., Kaushansky Kenneth, Thrombopoietin Signal Transduction Requires Functional JAK2, Not TYK2, 10.1074/jbc.274.19.13480
  4. Witthuhn Bruce A., Quelle Frederick W., Silvennoinen Olli, Yi Taolin, Tang Bo, Miura Osamu, Ihle James N., JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin, 10.1016/0092-8674(93)90414-l
  5. Royer Yohan, Staerk Judith, Costuleanu Marcel, Courtoy Pierre J., Constantinescu Stefan N., Janus Kinases Affect Thrombopoietin Receptor Cell Surface Localization and Stability, 10.1074/jbc.m501376200
  6. Baxter E Joanna, Scott Linda M, Campbell Peter J, East Clare, Fourouclas Nasios, Swanton Soheila, Vassiliou George S, Bench Anthony J, Boyd Elaine M, Curtin Natasha, Scott Mike A, Erber Wendy N, Green Anthony R, Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders, 10.1016/s0140-6736(05)71142-9
  7. James Chloé, Ugo Valérie, Le Couédic Jean-Pierre, Staerk Judith, Delhommeau François, Lacout Catherine, Garçon Loïc, Raslova Hana, Berger Roland, Bennaceur-Griscelli Annelise, Villeval Jean Luc, Constantinescu Stefan N., Casadevall Nicole, Vainchenker William, A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera, 10.1038/nature03546
  8. Kralovics Robert, Passamonti Francesco, Buser Andreas S., Teo Soon-Siong, Tiedt Ralph, Passweg Jakob R., Tichelli Andre, Cazzola Mario, Skoda Radek C., A Gain-of-Function Mutation ofJAK2in Myeloproliferative Disorders, 10.1056/nejmoa051113
  9. Levine Ross L., Wadleigh Martha, Cools Jan, Ebert Benjamin L., Wernig Gerlinde, Huntly Brian J.P., Boggon Titus J., Wlodarska Iwona, Clark Jennifer J., Moore Sandra, Adelsperger Jennifer, Koo Sumin, Lee Jeffrey C., Gabriel Stacey, Mercher Thomas, D’Andrea Alan, Fröhling Stefan, Döhner Konstanze, Marynen Peter, Vandenberghe Peter, Mesa Ruben A., Tefferi Ayalew, Griffin James D., Eck Michael J., Sellers William R., Meyerson Matthew, Golub Todd R., Lee Stephanie J., Gilliland D. Gary, Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis, 10.1016/j.ccr.2005.03.023
  10. Pietra D., Brisci A., Rumi E., Boggi S., Elena C., Pietrelli A., Bordoni R., Ferrari M., Passamonti F., De Bellis G., Cremonesi L., Cazzola M., Deep sequencing reveals double mutations in cis of MPL exon 10 in myeloproliferative neoplasms, 10.3324/haematol.2010.034793
  11. Nangalia J., Massie C.E., Baxter E.J., Nice F.L., Gundem G., Wedge D.C., Avezov E., Li J., Kollmann K., Kent D.G., Aziz A., Godfrey A.L., Hinton J., Martincorena I., Van Loo P., Jones A.V., Guglielmelli P., Tarpey P., Harding H.P., Fitzpatrick J.D., Goudie C.T., Ortmann C.A., Loughran S.J., Raine K., Jones D.R., Butler A.P., Teague J.W., O'Meara S., McLaren S., Bianchi M., Silber Y., Dimitropoulou D., Bloxham D., Mudie L., Maddison M., Robinson B., Keohane C., Maclean C., Hill K., Orchard K., Tauro S., Du M.-Q., Greaves M., Bowen D., Huntly B.J.P., Harrison C.N., Cross N.C.P., Ron D., Vannucchi A.M., Papaemmanuil E., Campbell P.J., Green A.R., Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2, 10.1056/nejmoa1312542
  12. Klampfl Thorsten, Gisslinger Heinz, Harutyunyan Ashot S., Nivarthi Harini, Rumi Elisa, Milosevic Jelena D., Them Nicole C.C., Berg Tiina, Gisslinger Bettina, Pietra Daniela, Chen Doris, Vladimer Gregory I., Bagienski Klaudia, Milanesi Chiara, Casetti Ilaria Carola, Sant'Antonio Emanuela, Ferretti Virginia, Elena Chiara, Schischlik Fiorella, Cleary Ciara, Six Melanie, Schalling Martin, Schönegger Andreas, Bock Christoph, Malcovati Luca, Pascutto Cristiana, Superti-Furga Giulio, Cazzola Mario, Kralovics Robert, Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms, 10.1056/nejmoa1311347
  13. Chachoua I., Pecquet C., El-Khoury M., Nivarthi H., Albu R.-I., Marty C., Gryshkova V., Defour J.-P., Vertenoeil G., Ngo A., Koay A., Raslova H., Courtoy P. J., Choong M. L., Plo I., Vainchenker W., Kralovics R., Constantinescu S. N., Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants, 10.1182/blood-2015-11-681932
  14. Rampal R., Al-Shahrour F., Abdel-Wahab O., Patel J. P., Brunel J.-P., Mermel C. H., Bass A. J., Pretz J., Ahn J., Hricik T., Kilpivaara O., Wadleigh M., Busque L., Gilliland D. G., Golub T. R., Ebert B. L., Levine R. L., Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis, 10.1182/blood-2014-02-554634
  15. JAK Inhibitor in CALR-Mutant Myelofibrosis, 10.1056/nejmc1400499
  16. Guglielmelli P., Biamonte F., Rotunno G., Artusi V., Artuso L., Bernardis I., Tenedini E., Pieri L., Paoli C., Mannarelli C., Fjerza R., Rumi E., Stalbovskaya V., Squires M., Cazzola M., Manfredini R., Harrison C., Tagliafico E., Vannucchi A. M., , Impact of mutational status on outcomes in myelofibrosis patients treated with ruxolitinib in the COMFORT-II study, 10.1182/blood-2013-11-536557
  17. Badrinarayan Preethi, Sastry G., Rational Approaches Towards Lead Optimization of Kinase Inhibitors: The Issue of Specificity, 10.2174/1381612811319260005
  18. Harrison Claire, Kiladjian Jean-Jacques, Al-Ali Haifa Kathrin, Gisslinger Heinz, Waltzman Roger, Stalbovskaya Viktoriya, McQuitty Mari, Hunter Deborah S., Levy Richard, Knoops Laurent, Cervantes Francisco, Vannucchi Alessandro M., Barbui Tiziano, Barosi Giovanni, JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis, 10.1056/nejmoa1110556
  19. Verstovsek Srdan, Mesa Ruben A., Gotlib Jason, Levy Richard S., Gupta Vikas, DiPersio John F., Catalano John V., Deininger Michael, Miller Carole, Silver Richard T., Talpaz Moshe, Winton Elliott F., Harvey Jimmie H., Arcasoy Murat O., Hexner Elizabeth, Lyons Roger M., Paquette Ronald, Raza Azra, Vaddi Kris, Erickson-Viitanen Susan, Koumenis Iphigenia L., Sun William, Sandor Victor, Kantarjian Hagop M., A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis, 10.1056/nejmoa1110557
  20. Vannucchi Alessandro M., Kiladjian Jean Jacques, Griesshammer Martin, Masszi Tamas, Durrant Simon, Passamonti Francesco, Harrison Claire N., Pane Fabrizio, Zachee Pierre, Mesa Ruben, He Shui, Jones Mark M., Garrett William, Li Jingjin, Pirron Ulrich, Habr Dany, Verstovsek Srdan, Ruxolitinib versus Standard Therapy for the Treatment of Polycythemia Vera, 10.1056/nejmoa1409002
  21. Verstovsek Srdan, Kantarjian Hagop, Mesa Ruben A., Pardanani Animesh D., Cortes-Franco Jorge, Thomas Deborah A., Estrov Zeev, Fridman Jordan S., Bradley Edward C., Erickson-Viitanen Susan, Vaddi Kris, Levy Richard, Tefferi Ayalew, Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in Myelofibrosis, 10.1056/nejmoa1002028
  22. Meyer S. C., Keller M. D., Woods B. A., LaFave L. M., Bastian L., Kleppe M., Bhagwat N., Marubayashi S., Levine R. L., Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis, 10.1182/blood-2014-03-560441
  23. Schepers H, JAKSTAT, 1, 13 (2012)
  24. Wierenga A. T. J., STAT5-induced self-renewal and impaired myelopoiesis of human hematopoietic stem/progenitor cells involves down-modulation of C/EBP , 10.1182/blood-2005-11-4608
  25. Zhang Q., Zhang Y., Diamond S., Boer J., Harris J. J., Li Y., Rupar M., Behshad E., Gardiner C., Collier P., Liu P., Burn T., Wynn R., Hollis G., Yeleswaram S., The Janus Kinase 2 Inhibitor Fedratinib Inhibits Thiamine Uptake: A Putative Mechanism for the Onset of Wernicke's Encephalopathy, 10.1124/dmd.114.058883
  26. Nakaya Y, Shide K, Naito H, Niwa T, Horio T, Miyake J, Shimoda K, Effect of NS-018, a selective JAK2V617F inhibitor, in a murine model of myelofibrosis, 10.1038/bcj.2013.73
  27. Ma L, Clayton J R, Walgren R A, Zhao B, Evans R J, Smith M C, Heinz-Taheny K M, Kreklau E L, Bloem L, Pitou C, Shen W, Strelow J M, Halstead C, Rempala M E, Parthasarathy S, Gillig J R, Heinz L J, Pei H, Wang Y, Stancato L F, Dowless M S, Iversen P W, Burkholder T P, Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F, 10.1038/bcj.2013.6
  28. Andraos Rita, Qian Zhiyan, Bonenfant Débora, Rubert Joëlle, Vangrevelinghe Eric, Scheufler Clemens, Marque Fanny, Régnier Catherine H., De Pover Alain, Ryckelynck Hugues, Bhagwat Neha, Koppikar Priya, Goel Aviva, Wyder Lorenza, Tavares Gisele, Baffert Fabienne, Pissot-Soldermann Carole, Manley Paul W., Gaul Christoph, Voshol Hans, Levine Ross L., Sellers William R., Hofmann Francesco, Radimerski Thomas, Modulation of Activation-Loop Phosphorylation by JAK Inhibitors Is Binding Mode Dependent, 10.1158/2159-8290.cd-11-0324
  29. Feng J, Witthuhn B A, Matsuda T, Kohlhuber F, Kerr I M, Ihle J N, Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop., 10.1128/mcb.17.5.2497
  30. Pratilas C. A., Taylor B. S., Ye Q., Viale A., Sander C., Solit D. B., Rosen N., V600EBRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway, 10.1073/pnas.0900780106
  31. Hatzivassiliou Georgia, Song Kyung, Yen Ivana, Brandhuber Barbara J., Anderson Daniel J., Alvarado Ryan, Ludlam Mary J. C., Stokoe David, Gloor Susan L., Vigers Guy, Morales Tony, Aliagas Ignacio, Liu Bonnie, Sideris Steve, Hoeflich Klaus P., Jaiswal Bijay S., Seshagiri Somasekar, Koeppen Hartmut, Belvin Marcia, Friedman Lori S., Malek Shiva, RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth, 10.1038/nature08833
  32. Koppikar Priya, Bhagwat Neha, Kilpivaara Outi, Manshouri Taghi, Adli Mazhar, Hricik Todd, Liu Fan, Saunders Lindsay M., Mullally Ann, Abdel-Wahab Omar, Leung Laura, Weinstein Abby, Marubayashi Sachie, Goel Aviva, Gönen Mithat, Estrov Zeev, Ebert Benjamin L., Chiosis Gabriela, Nimer Stephen D., Bernstein Bradley E., Verstovsek Srdan, Levine Ross L., Heterodimeric JAK–STAT activation as a mechanism of persistence to JAK2 inhibitor therapy, 10.1038/nature11303
  33. Meyer Sara C., Keller Matthew D., Chiu Sophia, Koppikar Priya, Guryanova Olga A., Rapaport Franck, Xu Ke, Manova Katia, Pankov Dmitry, O’Reilly Richard J., Kleppe Maria, McKenney Anna Sophia, Shih Alan H., Shank Kaitlyn, Ahn Jihae, Papalexi Eftymia, Spitzer Barbara, Socci Nick, Viale Agnes, Mandon Emeline, Ebel Nicolas, Andraos Rita, Rubert Joëlle, Dammassa Ernesta, Romanet Vincent, Dölemeyer Arno, Zender Michael, Heinlein Melanie, Rampal Raajit, Weinberg Rona Singer, Hoffman Ronald, Sellers William R., Hofmann Francesco, Murakami Masato, Baffert Fabienne, Gaul Christoph, Radimerski Thomas, Levine Ross L., CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms, 10.1016/j.ccell.2015.06.006
  34. Marty C., Saint-Martin C., Pecquet C., Grosjean S., Saliba J., Mouton C., Leroy E., Harutyunyan A. S., Abgrall J.-F., Favier R., Toussaint A., Solary E., Kralovics R., Constantinescu S. N., Najman A., Vainchenker W., Plo I., Bellanne-Chantelot C., Germ-line JAK2 mutations in the kinase domain are responsible for hereditary thrombocytosis and are resistant to JAK2 and HSP90 inhibitors, 10.1182/blood-2013-05-504555
  35. Liu Yi, Gray Nathanael S, Rational design of inhibitors that bind to inactive kinase conformations, 10.1038/nchembio799
  36. Nagar B, Cancer Res, 62, 4236 (2002)
  37. Wu Shuo-Chieh, Li Loretta S., Kopp Nadja, Montero Joan, Chapuy Bjoern, Yoda Akinori, Christie Amanda L., Liu Huiyun, Christodoulou Alexandra, van Bodegom Diederik, van der Zwet Jordy, Layer Jacob V., Tivey Trevor, Lane Andrew A., Ryan Jeremy A., Ng Samuel Y., DeAngelo Daniel J., Stone Richard M., Steensma David, Wadleigh Martha, Harris Marian, Mandon Emeline, Ebel Nicolas, Andraos Rita, Romanet Vincent, Dölemeyer Arno, Sterker Dario, Zender Michael, Rodig Scott J., Murakami Masato, Hofmann Francesco, Kuo Frank, Eck Michael J., Silverman Lewis B., Sallan Stephen E., Letai Anthony, Baffert Fabienne, Vangrevelinghe Eric, Radimerski Thomas, Gaul Christoph, Weinstock David M., Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia, 10.1016/j.ccell.2015.06.005
  38. Ma Dik-Lung, Chan Daniel Shiu-Hin, Wei Guo, Zhong Hai-Jing, Yang Hui, Leung Lai To, Gullen Elizabeth A., Chiu Pauline, Cheng Yung-Chi, Leung Chung-Hang, Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library, 10.1039/c4cc04498c
  39. Losdyck Elisabeth, Hornakova Tekla, Springuel Lorraine, Degryse Sandrine, Gielen Olga, Cools Jan, Constantinescu Stefan N., Flex Elisabetta, Tartaglia Marco, Renauld Jean-Christophe, Knoops Laurent, Distinct Acute Lymphoblastic Leukemia (ALL)-associated Janus Kinase 3 (JAK3) Mutants Exhibit Different Cytokine-Receptor Requirements and JAK Inhibitor Specificities, 10.1074/jbc.m115.670224
  40. Zhang Jianming, Yang Priscilla L., Gray Nathanael S., Targeting cancer with small molecule kinase inhibitors, 10.1038/nrc2559
  41. Cowan-Jacob Sandra W, Möbitz Henrik, Fabbro Doriano, Structural biology contributions to tyrosine kinase drug discovery, 10.1016/j.ceb.2009.01.012
  42. Cowan-Jacob Sandra W, Jahnke Wolfgang, Knapp Stefan, Novel approaches for targeting kinases: allosteric inhibition, allosteric activation and pseudokinases, 10.4155/fmc.13.216
  43. Adrián Francisco J, Ding Qiang, Sim Taebo, Velentza Anastasia, Sloan Christine, Liu Yi, Zhang Guobao, Hur Wooyoung, Ding Sheng, Manley Paul, Mestan Jürgen, Fabbro Doriano, Gray Nathanael S, Allosteric inhibitors of Bcr-abl–dependent cell proliferation, 10.1038/nchembio760
  44. Jatiani S. S., Cosenza S. C., Reddy M. V. R., Ha J. H., Baker S. J., Samanta A. K., Olnes M. J., Pfannes L., Sloand E. M., Arlinghaus R. B., Reddy E. P., A Non-ATP-Competitive Dual Inhibitor of JAK2V617F and BCR-ABLT315I Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition, 10.1177/1947601910371337
  45. Lipka D. B., Hoffmann L. S., Heidel F., Markova B., Blum M.-C., Breitenbuecher F., Kasper S., Kindler T., Levine R. L., Huber C., Fischer T., LS104, a non-ATP-competitive small-molecule inhibitor of JAK2, is potently inducing apoptosis in JAK2V617F-positive cells, 10.1158/1535-7163.mct-07-2215
  46. Samanta A. K., Chakraborty S. N., Wang Y., Schlette E., Reddy E. P., Arlinghaus R. B., Destabilization of Bcr-Abl/Jak2 Network by a Jak2/Abl Kinase Inhibitor ON044580 Overcomes Drug Resistance in Blast Crisis Chronic Myelogenous Leukemia (CML), 10.1177/1947601910372232
  47. Dusa Alexandra, Mouton Céline, Pecquet Christian, Herman Murielle, Constantinescu Stefan N., JAK2 V617F Constitutive Activation Requires JH2 Residue F595: A Pseudokinase Domain Target for Specific Inhibitors, 10.1371/journal.pone.0011157
  48. Toms Angela V, Deshpande Anagha, McNally Randall, Jeong Youngjee, Rogers Julia M, Kim Chae Un, Gruner Sol M, Ficarro Scott B, Marto Jarrod A, Sattler Martin, Griffin James D, Eck Michael J, Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases, 10.1038/nsmb.2673
  49. Hammarén Henrik M., Ungureanu Daniela, Grisouard Jean, Skoda Radek C., Hubbard Stevan R., Silvennoinen Olli, ATP binding to the pseudokinase domain of JAK2 is critical for pathogenic activation, 10.1073/pnas.1423201112
  50. Leroy E., Dusa A., Colau D., Motamedi A., Cahu X., Mouton C., Huang L. J., Shiau A. K., Constantinescu S. N., Uncoupling JAK2 V617F activation from cytokine-induced signalling by modulation of JH2  C helix, 10.1042/bcj20160085
  51. Saharinen Pipsa, Silvennoinen Olli, The Pseudokinase Domain Is Required for Suppression of Basal Activity of Jak2 and Jak3 Tyrosine Kinases and for Cytokine-inducible Activation of Signal Transduction, 10.1074/jbc.m205156200
  52. Yeh T. C., Dondi E., Uze G., Pellegrini S., A dual role for the kinase-like domain of the tyrosine kinase Tyk2 in interferon-alpha signaling, 10.1073/pnas.160130297
  53. Chen M., Cheng A., Candotti F., Zhou Y.-J., Hymel A., Fasth A., Notarangelo L. D., O'Shea J. J., Complex Effects of Naturally Occurring Mutations in the JAK3 Pseudokinase Domain: Evidence for Interactions between the Kinase and Pseudokinase Domains, 10.1128/mcb.20.3.947-956.2000
  54. Shan Yibing, Gnanasambandan Kavitha, Ungureanu Daniela, Kim Eric T, Hammarén Henrik, Yamashita Kazuo, Silvennoinen Olli, Shaw David E, Hubbard Stevan R, Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase, 10.1038/nsmb.2849
  55. Lupardus P. J., Ultsch M., Wallweber H., Bir Kohli P., Johnson A. R., Eigenbrot C., Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition, 10.1073/pnas.1401180111
  56. Bandaranayake Rajintha M, Ungureanu Daniela, Shan Yibing, Shaw David E, Silvennoinen Olli, Hubbard Stevan R, Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F, 10.1038/nsmb.2348
  57. Ungureanu Daniela, Wu Jinhua, Pekkala Tuija, Niranjan Yashavanthi, Young Clifford, Jensen Ole N, Xu Chong-Feng, Neubert Thomas A, Skoda Radek C, Hubbard Stevan R, Silvennoinen Olli, The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling, 10.1038/nsmb.2099
  58. Hasan S., Lacout C., Marty C., Cuingnet M., Solary E., Vainchenker W., Villeval J.-L., JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a competitive advantage that is hampered by IFN , 10.1182/blood-2013-04-498956
  59. Bhagwat Neha, Koppikar Priya, Keller Matthew, Marubayashi Sachie, Shank Kaitlyn, Rampal Raajit, Qi Jun, Kleppe Maria, Patel Hardik J., Shah Smit K., Taldone Tony, Bradner James E., Chiosis Gabriela, Levine Ross L., Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms, 10.1182/blood-2014-01-547760
  60. Tokarski John S., Zupa-Fernandez Adriana, Tredup Jeffrey A., Pike Kristen, Chang ChiehYing, Xie Dianlin, Cheng Lihong, Pedicord Donna, Muckelbauer Jodi, Johnson Stephen R., Wu Sophie, Edavettal Suzanne C., Hong Yang, Witmer Mark R., Elkin Lisa L., Blat Yuval, Pitts William J., Weinstein David S., Burke James R., Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by Pharmacological Stabilization of Its Pseudokinase Domain, 10.1074/jbc.m114.619502
  61. Davis Mindy I, Hunt Jeremy P, Herrgard Sanna, Ciceri Pietro, Wodicka Lisa M, Pallares Gabriel, Hocker Michael, Treiber Daniel K, Zarrinkar Patrick P, Comprehensive analysis of kinase inhibitor selectivity, 10.1038/nbt.1990
  62. Min Xiaoshan, Ungureanu Daniela, Maxwell Sarah, Hammarén Henrik, Thibault Steve, Hillert Ellin-Kristina, Ayres Merrill, Greenfield Brad, Eksterowicz John, Gabel Chris, Walker Nigel, Silvennoinen Olli, Wang Zhulun, Structural and Functional Characterization of the JH2 Pseudokinase Domain of JAK Family Tyrosine Kinase 2 (TYK2), 10.1074/jbc.m115.672048
  63. Dusa Alexandra, Staerk Judith, Elliott Joanne, Pecquet Christian, Poirel Hélène A., Johnston James A., Constantinescu Stefan N., Substitution of Pseudokinase Domain Residue Val-617 by Large Non-polar Amino Acids Causes Activation of JAK2, 10.1074/jbc.m709302200
  64. Zhao Lequn, Dong Hongyun, Zhang Cheng Cheng, Kinch Lisa, Osawa Mitsujiro, Iacovino Michelina, Grishin Nikolai V., Kyba Michael, Huang Lily Jun-shen, A JAK2 Interdomain Linker Relays Epo Receptor Engagement Signals to Kinase Activation, 10.1074/jbc.m109.011387
  65. Liu Qingsong, Sabnis Yogesh, Zhao Zheng, Zhang Tinghu, Buhrlage Sara J., Jones Lyn H., Gray Nathanael S., Developing Irreversible Inhibitors of the Protein Kinase Cysteinome, 10.1016/j.chembiol.2012.12.006
  66. Leproult Emeline, Barluenga Sofia, Moras Dino, Wurtz Jean-Marie, Winssinger Nicolas, Cysteine Mapping in Conformationally Distinct Kinase Nucleotide Binding Sites: Application to the Design of Selective Covalent Inhibitors, 10.1021/jm101396q
  67. Tan Li, Akahane Koshi, McNally Randall, Reyskens Kathleen M. S. E., Ficarro Scott B., Liu Suhu, Herter-Sprie Grit S., Koyama Shohei, Pattison Michael J., Labella Katherine, Johannessen Liv, Akbay Esra A., Wong Kwok-Kin, Frank David A., Marto Jarrod A., Look Thomas A., Arthur J. Simon C., Eck Michael J., Gray Nathanael S., Development of Selective Covalent Janus Kinase 3 Inhibitors, 10.1021/acs.jmedchem.5b00710
  68. Goedken Eric R., Argiriadi Maria A., Banach David L., Fiamengo Bryan A., Foley Sage E., Frank Kristine E., George Jonathan S., Harris Christopher M., Hobson Adrian D., Ihle David C., Marcotte Douglas, Merta Philip J., Michalak Mark E., Murdock Sara E., Tomlinson Medha J., Voss Jeffrey W., Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol, 10.1074/jbc.m114.595181
  69. Yun C.-H., Mengwasser K. E., Toms A. V., Woo M. S., Greulich H., Wong K.-K., Meyerson M., Eck M. J., The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP, 10.1073/pnas.0709662105
  70. Zhang Jianming, Adrián Francisco J., Jahnke Wolfgang, Cowan-Jacob Sandra W., Li Allen G., Iacob Roxana E., Sim Taebo, Powers John, Dierks Christine, Sun Fangxian, Guo Gui-Rong, Ding Qiang, Okram Barun, Choi Yongmun, Wojciechowski Amy, Deng Xianming, Liu Guoxun, Fendrich Gabriele, Strauss André, Vajpai Navratna, Grzesiek Stephan, Tuntland Tove, Liu Yi, Bursulaya Badry, Azam Mohammad, Manley Paul W., Engen John R., Daley George Q., Warmuth Markus, Gray Nathanael S., Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors, 10.1038/nature08675
  71. Lu X., Levine R., Tong W., Wernig G., Pikman Y., Zarnegar S., Gilliland D. G., Lodish H., Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation, 10.1073/pnas.0509714102
  72. Lu Xiaohui, Huang Lily Jun-Shen, Lodish Harvey F., Dimerization by a Cytokine Receptor Is Necessary for Constitutive Activation of JAK2V617F, 10.1074/jbc.m707125200
  73. Staerk Judith, Defour Jean-Philippe, Pecquet Christian, Leroy Emilie, Antoine-Poirel Hélène, Brett Ian, Itaya Miki, Smith Steven O, Vainchenker William, Constantinescu Stefan N, Orientation-specific signalling by thrombopoietin receptor dimers : Orientation-specific TpoR signalling, 10.1038/emboj.2011.315
  74. Matthews E. E., Thevenin D., Rogers J. M., Gotow L., Lira P. D., Reiter L. A., Brissette W. H., Engelman D. M., Thrombopoietin receptor activation: transmembrane helix dimerization, rotation, and allosteric modulation, 10.1096/fj.10-178673
  75. Seubert Nadine, Royer Yohan, Staerk Judith, Kubatzky Katharina F, Moucadel Virginie, Krishnakumar Shyam, Smith Steven O, Constantinescu Stefan N, Active and Inactive Orientations of the Transmembrane and Cytosolic Domains of the Erythropoietin Receptor Dimer, 10.1016/s1097-2765(03)00389-7
  76. Moraga Ignacio, Wernig Gerlinde, Wilmes Stephan, Gryshkova Vitalina, Richter Christian P., Hong Wan-Jen, Sinha Rahul, Guo Feng, Fabionar Hyna, Wehrman Tom S., Krutzik Peter, Demharter Samuel, Plo Isabelle, Weissman Irving L., Minary Peter, Majeti Ravindra, Constantinescu Stefan N., Piehler Jacob, Garcia K. Christopher, Tuning Cytokine Receptor Signaling by Re-orienting Dimer Geometry with Surrogate Ligands, 10.1016/j.cell.2015.02.011
  77. Ferrao Ryan, Wallweber Heidi J.A., Ho Hoangdung, Tam Christine, Franke Yvonne, Quinn John, Lupardus Patrick J., The Structural Basis for Class II Cytokine Receptor Recognition by JAK1, 10.1016/j.str.2016.03.023
  78. Wallweber Heidi J A, Tam Christine, Franke Yvonne, Starovasnik Melissa A, Lupardus Patrick J, Structural basis of recognition of interferon-α receptor by tyrosine kinase 2, 10.1038/nsmb.2807
  79. Bergeron Jean, Frank Philippe G., Scales Damon, Meng Qiang-Hua, Castro Graciela, Marcel Yves L., Apolipoprotein A-I Conformation in Reconstituted Discoidal Lipoproteins Varying in Phospholipid and Cholesterol Content, 10.1074/jbc.270.46.27429
  80. Haan Claude, Is'harc Hayaatun, Hermanns Heike M., Schmitz-Van de Leur Hildegard, Kerr Ian M., Heinrich Peter C., Grötzinger Joachim, Behrmann Iris, Mapping of a Region within the N Terminus of Jak1 Involved in Cytokine Receptor Interaction, 10.1074/jbc.m106135200
  81. Kohlhuber F, Rogers N C, Watling D, Feng J, Guschin D, Briscoe J, Witthuhn B A, Kotenko S V, Pestka S, Stark G R, Ihle J N, Kerr I M, A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses., 10.1128/mcb.17.2.695
  82. Zhao Yanming, Wagner Fred, Frank Stuart J., Kraft Andrew S., The Amino-terminal Portion of the JAK2 Protein Kinase Is Necessary For Binding and Phosphorylation of the Granulocyte-Macrophage Colony-stimulating Factor Receptor β Chain, 10.1074/jbc.270.23.13814
  83. Wernig G., Gonneville J. R., Crowley B. J., Rodrigues M. S., Reddy M. M., Hudon H. E., Walz C., Reiter A., Podar K., Royer Y., Constantinescu S. N., Tomasson M. H., Griffin J. D., Gilliland D. G., Sattler M., The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes, 10.1182/blood-2007-07-102186
  84. Zhao Lequn, Ma Yue, Seemann Joachim, Huang Lily Jun-shen, A regulating role of the JAK2 FERM domain in hyperactivation of JAK2(V617F), 10.1042/bj20090615
  85. McNally Randall, Toms Angela V., Eck Michael J., Crystal Structure of the FERM-SH2 Module of Human Jak2, 10.1371/journal.pone.0156218
  86. Cacalano N. A., Autosomal SCID caused by a point mutation in the N-terminus of Jak3: mapping of the Jak3-receptor interaction domain, 10.1093/emboj/18.6.1549
  87. O’Sullivan J. M., McLornan D. P., Harrison C. N., Safety considerations when treating myelofibrosis, 10.1080/14740338.2016.1185414
  88. Genovese Mark C., Kremer Joel, Zamani Omid, Ludivico Charles, Krogulec Marek, Xie Li, Beattie Scott D., Koch Alisa E., Cardillo Tracy E., Rooney Terence P., Macias William L., de Bono Stephanie, Schlichting Douglas E., Smolen Josef S., Baricitinib in Patients with Refractory Rheumatoid Arthritis, 10.1056/nejmoa1507247
  89. Plimack E. R., LoRusso P. M., McCoon P., Tang W., Krebs A. D., Curt G., Eckhardt S. G., AZD1480: A Phase I Study of a Novel JAK2 Inhibitor in Solid Tumors, 10.1634/theoncologist.2013-0198
  90. Seavey M. M., Lu L. D., Stump K. L., Wallace N. H., Hockeimer W., O'Kane T. M., Ruggeri B. A., Dobrzanski P., Therapeutic Efficacy of CEP-33779, a Novel Selective JAK2 Inhibitor, in a Mouse Model of Colitis-Induced Colorectal Cancer, 10.1158/1535-7163.mct-11-0951
  91. Baffert F., Regnier C. H., De Pover A., Pissot-Soldermann C., Tavares G. A., Blasco F., Brueggen J., Chene P., Drueckes P., Erdmann D., Furet P., Gerspacher M., Lang M., Ledieu D., Nolan L., Ruetz S., Trappe J., Vangrevelinghe E., Wartmann M., Wyder L., Hofmann F., Radimerski T., Potent and Selective Inhibition of Polycythemia by the Quinoxaline JAK2 Inhibitor NVP-BSK805, 10.1158/1535-7163.mct-10-0053
  92. Duan Yankun, Chen Lin, Chen Yongheng, Fan Xue-gong, c-Src Binds to the Cancer Drug Ruxolitinib with an Active Conformation, 10.1371/journal.pone.0106225
  93. Syed Rashid S., Reid Scott W., Li Cuiwei, Cheetham Janet C., Aoki Kenneth H., Liu Beishan, Zhan Hangjun, Osslund Timothy D., Chirino Arthur J., Zhang Jiandong, Finer-Moore Janet, Elliott Steven, Sitney Karen, Katz Bradley A., Matthews David J., Wendoloski John J., Egrie Joan, Stroud Robert M., 10.1038/26773
  94. Li Qingxin, Lei Wong Ying, Yueqi Lee Michelle, Li Yan, Kang CongBao, Solution structure of the transmembrane domain of the mouse erythropoietin receptor in detergent micelles, 10.1038/srep13586
  95. Abdelrahman Ramy A., Begna Kebede H., Al-Kali Aref, Hogan William J., Litzow Mark R., Pardanani Animesh, Tefferi Ayalew, Momelotinib treatment-emergent neuropathy: prevalence, risk factors and outcome in 100 patients with myelofibrosis, 10.1111/bjh.13262
  96. Purandare A V, McDevitt T M, Wan H, You D, Penhallow B, Han X, Vuppugalla R, Zhang Y, Ruepp S U, Trainor G L, Lombardo L, Pedicord D, Gottardis M M, Ross-Macdonald P, de Silva H, Hosbach J, Emanuel S L, Blat Y, Fitzpatrick E, Taylor T L, McIntyre K W, Michaud E, Mulligan C, Lee F Y, Woolfson A, Lasho T L, Pardanani A, Tefferi A, Lorenzi M V, Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2, 10.1038/leu.2011.292
  97. Hexner Elizabeth O., Mascarenhas John, Prchal Josef, Roboz Gail J., Baer Maria R., Ritchie Ellen K., Leibowitz David, Demakos Erin P., Miller Crystal, Siuty James, Kleczko Jill, Price Leah, Jeschke Grace, Weinberg Rona, Basu Titiksha, Pahl Heike L., Orazi Attilio, Najfeld Vesna, Marchioli Roberto, Goldberg Judith D., Silverman Lewis R., Hoffman Ronald, Phase I dose escalation study of lestaurtinib in patients with myelofibrosis, 10.3109/10428194.2014.1001986
  98. Verstovsek Srdan, Hoffman Ronald, Mascarenhas John, Soria Jean-Charles, Bahleda Ratislav, McCoon Patricia, Tang Weifeng, Cortes Jorge, Kantarjian Hagop, Ribrag Vincent, A phase I, open-label, multi-center study of the JAK2 inhibitor AZD1480 in patients with myelofibrosis, 10.1016/j.leukres.2014.11.018
  99. Komrokji R. S., Seymour J. F., Roberts A. W., Wadleigh M., To L. B., Scherber R., Turba E., Dorr A., Zhu J., Wang L., Granston T., Campbell M. S., Mesa R. A., Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis, 10.1182/blood-2013-02-484832
  100. Verstovsek Srdan, Tam Constantine S., Wadleigh Martha, Sokol Lubomir, Smith Catherine C., Bui Lynne A., Song Chunyan, Clary Douglas O., Olszynski Patrycja, Cortes Jorge, Kantarjian Hagop, Shah Neil P., Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor, 10.1016/j.leukres.2013.12.006
  101. Ringel Frauke, Kaeda Jaspal, Schwarz Michaela, Oberender Christian, Grille Peggy, Dörken Bernd, Marque Fanny, Manley Paul W., Radimerski Thomas, le Coutre Philipp, Effects of Jak2 Type 1 Inhibitors NVP-BSK805 and NVP-BVB808 on Jak2 Mutation-Positive and Bcr-Abl-Positive Cell Lines, 10.1159/000356784
  102. Geissler Klaus, Jäger Eva, Barna Agnes, Sliwa Thamer, Knöbl Paul, Schwarzinger Ilse, Gisslinger Heinz, Valent Peter, In vitroandin vivoeffects of JAK2 inhibition in chronic myelomonocytic leukemia, 10.1111/ejh.12773
  103. Miyamoto N, Sugita K, Goi K, Inukai T, Iijima K, Tezuka T, Kojika S, Nakamura M, Kagami K, Nakazawa S, The JAK2 inhibitor AG490 predominantly abrogates the growth of human B-precursor leukemic cells with 11q23 translocation or Philadelphia chromosome, 10.1038/sj.leu.2402260