Skip to main content
SpringerLink
Log in

The Use of JAK-Specific Inhibitors as Chemical Biology Tools

  • Protocol
  • First Online:
JAK-STAT Signalling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 967))

Abstract

The JAK family of protein tyrosine kinases are now recognized as important participants in a wide range of pathologies, from cancer to inflammatory diseases. In the last decade, the drive to develop drugs targeting members of this family has begun to deliver a panel of small molecule inhibitors of JAK family members, with a range of potencies and specificities. A number of these compounds have already found widespread use as biochemical tools in the elucidation of JAK activity in specific signaling and disease processes; however, many of the first generation compounds are poorly characterized with suboptimal potencies and selectivities.

Herein, we present the data for those small molecule JAK inhibitors that have been described in the peer-reviewed literature and the benefits and potential issues that may be associated with the use of these tool compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (1997) A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 278:1309–1312

    Article  PubMed  CAS  Google Scholar 

  2. Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O’Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC (2005) The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res 65:2662–2667

    Article  PubMed  CAS  Google Scholar 

  3. Bousquet M, Quelen C, De Mas V, Duchayne E, Roquefeuil B, Delsol G, Laurent G, Dastugue N, Brousset P (2005) The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. Oncogene 24:7248–7252

    Article  PubMed  CAS  Google Scholar 

  4. Murati A, Gelsi-Boyer V, Adelaide J, Perot C, Talmant P, Giraudier S, Lode L, Letessier A, Delaval B, Brunel V, Imbert M, Garand R, Xerri L, Birnbaum D, Mozziconacci MJ, Chaffanet M (2005) PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. Leukemia 19:1692–1696

    Article  PubMed  CAS  Google Scholar 

  5. Griesinger F, Hennig H, Hillmer F, Podleschny M, Steffens R, Pies A, Wormann B, Haase D, Bohlander SK (2005) A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia. Genes Chromosomes Cancer 44:329–333

    Article  PubMed  CAS  Google Scholar 

  6. Mark HF, Sotomayor EA, Nelson M, Chaves F, Sanger WG, Kaleem Z, Caughron SK (2006) Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation disrupting the Janus kinase 2 (JAK2) gene. Exp Mol Pathol 81:217–223

    Article  PubMed  CAS  Google Scholar 

  7. Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, Tasian SK, Loh ML, Su X, Liu W, Devidas M, Atlas SR, Chen I-M, Clifford RJ, Gerhard DS, Carroll WL, Reaman GH, Smith M, Downing JR, Hunger SP, Willman CL (2009) JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci 106:9414–9418

    Article  PubMed  CAS  Google Scholar 

  8. Frye SV (2010) The art of the chemical probe. Nat Chem Biol 6:159–161

    Article  PubMed  CAS  Google Scholar 

  9. Cohen P (2009) Guidelines for the effective use of chemical inhibitors of protein function to understand their roles in cell regulation. Biochem J 425:53–54

    Article  PubMed  Google Scholar 

  10. Meydan N, Grunberger T, Dadi H, Shahar M, Arpaia E, Lapidot Z, Leeder JS, Freedman M, Cohen A, Gazit A, Levitzki A, Roifman CM (1996) Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature 379:645–648

    Article  PubMed  CAS  Google Scholar 

  11. Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ, Sawyer PS, Perry BD, Brissette WH, McCurdy SP, Kudlacz EM, Conklyn MJ, Elliott EA, Koslov ER, Fisher MB, Strelevitz TJ, Yoon K, Whipple DA, Sun J, Munchhof MJ, Doty JL, Casavant JM, Blumenkopf TA, Hines M, Brown MF, Lillie BM, Subramanyam C, Shang-Poa C, Milici AJ, Beckius GE, Moyer JD, Su C, Woodworth TG, Gaweco AS, Beals CR, Littman BH, Fisher DA, Smith JF, Zagouras P, Magna HA, Saltarelli MJ, Johnson KS, Nelms LF, Des Etages SG, Hayes LS, Kawabata TT, Finco-Kent D, Baker DL, Larson M, Si MS, Paniagua R, Higgins J, Holm B, Reitz B, Zhou YJ, Morris RE, O’Shea JJ, Borie DC (2003) Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 302:875–878

    Article  PubMed  CAS  Google Scholar 

  12. Kleinberger-Doron N, Shelah N, Capone R, Gazit A, Levitzki A (1998) Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at late G1 and S phase. Exp Cell Res 241:340–351

    Article  PubMed  CAS  Google Scholar 

  13. Oda Y, Renaux B, Bjorge J, Saifeddine M, Fujita DJ, Hollenberg MD (1999) cSrc is a major cytosolic tyrosine kinase in vascular tissue. Can J Physiol Pharmacol 77:606–617

    Article  PubMed  CAS  Google Scholar 

  14. Osherov N, Gazit A, Gilon C, Levitzki A (1993) Selective inhibition of the epidermal growth factor and HER2/neu receptors by tyrphostins. J Biol Chem 268:11134–11142

    PubMed  CAS  Google Scholar 

  15. Grunberger T, Demin P, Rounova O, Sharfe N, Cimpean L, Dadi H, Freywald A, Estrov Z, Roifman CM (2003) Inhibition of acute lymphoblastic and myeloid leukemias by a novel kinase inhibitor. Blood 102:4153–4158

    PubMed  CAS  Google Scholar 

  16. Kiss R, Polgar T, Kirabo A, Sayyah J, Figueroa NC, List AF, Sokol L, Zuckerman KS, Gali M, Bisht KS, Sayeski PP, Keseru GM (2009) Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening. Bioorg Med Chem Lett 19:3598–3601

    Article  PubMed  CAS  Google Scholar 

  17. Duan Z, Bradner J, Greenberg E, Mazitschek R, Foster R, Mahoney J, Seiden MV (2007) 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 72:1137–1145

    Article  PubMed  CAS  Google Scholar 

  18. Sayyah J, Magis A, Ostrov DA, Allan RW, Braylan RC, Sayeski PP (2008) Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth. Mol Cancer Ther 7:2308–2318

    Article  PubMed  CAS  Google Scholar 

  19. Sandberg EM, Ma X, He K, Frank SJ, Ostrov DA, Sayeski PP (2005) Identification of 1,2,3,4,5,6-hexabromocyclohexane as a small molecule inhibitor of jak2 tyrosine kinase autophosphorylation (correction of autophophorylation). J Med Chem 48:2526–2533

    Article  PubMed  CAS  Google Scholar 

  20. Sudbeck EA, Liu X-P, Narla RK, Mahajan S, Ghosh S, Mao C, Uckun FM (1999) Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents. Clin Cancer Res 5:1569–1582

    PubMed  CAS  Google Scholar 

  21. Changelian PS, Moshinsky D, Kuhn CF, Flanagan ME, Munchhof MJ, Harris TM, Whipple DA, Doty JL, Sun J, Kent CR, Magnuson KS, Perregaux DG, Sawyer PS, Kudlacz EM (2008) The specificity of JAK3 kinase inhibitors. Blood 111:2155–2157

    Article  PubMed  CAS  Google Scholar 

  22. Torr V, Culbert EJ (2000) Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett 10:575–579

    Article  PubMed  Google Scholar 

  23. Stepkowski SM, Kao J, Wang ME, Tejpal N, Podder H, Furian L, Dimmock J, Jha A, Das U, Kahan BD, Kirken RA (2005) The Mannich base NC1153 promotes long-term allograft survival and spares the recipient from multiple toxicities. J Immunol 175:4236–4246

    PubMed  CAS  Google Scholar 

  24. Stepkowski SM, Erwin-Cohen RA, Behbod F, Wang ME, Qu X, Tejpal N, Nagy ZS, Kahan BD, Kirken RA (2002) Selective inhibitor of Janus tyrosine kinase 3, PNU156804, prolongs allograft survival and acts synergistically with cyclosporine but additively with rapamycin. Blood 99:680–689

    Article  PubMed  CAS  Google Scholar 

  25. Lee BI, Ahn HJ, Han KC, Ahn DR, Shin D (2011) Pyrogallin, an ATP-competitive inhibitor of JAK3. Bull Korean Chem Soc 32:1077–1079

    Article  CAS  Google Scholar 

  26. Kim BH, Jee JG, Yin CH, Sandoval C, Jayabose S, Kitamura D, Bach EA, Baeg GH (2010) NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3. Mol Cancer 9:36

    Article  PubMed  Google Scholar 

  27. Thompson JE, Cubbon RM, Cummings RT, Wicker LS, Frankshun R, Cunningham BR, Cameron PM, Meinke PT, Liverton N, Weng Y, DeMartino JA (2002) Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor. Bioorg Med Chem Lett 12:1219–1223

    Article  PubMed  CAS  Google Scholar 

  28. Peifer C, Alessi DR (2008) Small-molecule inhibitors of PDK1. ChemMedChem 3:1810–1838

    Article  PubMed  CAS  Google Scholar 

  29. Hancock MK, Lebakken CS, Wang J, Bi K (2010) Multi-pathway cellular analysis of compound selectivity. Mol Biosyst 6:1834–1843

    Article  PubMed  CAS  Google Scholar 

  30. Mathur A, Mo JR, Kraus M, O’Hare E, Sinclair P, Young J, Zhao S, Wang Y, Kopinja J, Qu X, Reilly J, Walker D, Xu L, Aleksandrowicz D, Marshall G, Scott ML, Kohl NE, Bachman E (2009) An inhibitor of Janus kinase 2 prevents polycythemia in mice. Biochem Pharmacol 78:382–389

    Article  PubMed  CAS  Google Scholar 

  31. Chen JJ, Thakur KD, Clark MP, Laughlin SK, George KM, Bookland RG, Davis JR, Cabrera EJ, Easwaran V, De B, George Zhang Y (2006) Development of pyrimidine-based inhibitors of Janus tyrosine kinase 3. Bioorg Med Chem Lett 16:5633–5638

    Article  PubMed  CAS  Google Scholar 

  32. Clark MP, George KM, Bookland RG, Chen J, Laughlin SK, Thakur KD, Lee W, Davis JR, Cabrera EJ, Brugel TA, VanRens JC, Laufersweiler MJ, Maier JA, Sabat MP, Golebiowski A, Easwaran V, Webster ME, De B, Zhang G (2007) Development of new pyrrolopyrimidine-based inhibitors of Janus kinase 3 (JAK3). Bioorg Med Chem Lett 17:1250–1253

    Article  PubMed  CAS  Google Scholar 

  33. Adams C, Aldous DJ, Amendola S, Bamborough P, Bright C, Crowe S, Eastwood P, Fenton G, Foster M, Harrison TK, King S, Lai J, Lawrence C, Letallec JP, McCarthy C, Moorcroft N, Page K, Rao S, Redford J, Sadiq S, Smith K, Souness JE, Thurairatnam S, Vine M, Wyman B (2003) Mapping the kinase domain of Janus Kinase 3. Bioorg Med Chem Lett 13:3105–3110

    Article  PubMed  CAS  Google Scholar 

  34. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790

    Article  PubMed  CAS  Google Scholar 

  35. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D’Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397

    Article  PubMed  CAS  Google Scholar 

  36. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, Garcon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144–1148

    Article  PubMed  CAS  Google Scholar 

  37. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061

    PubMed  CAS  Google Scholar 

  38. Verstovsek S (2009) Therapeutic potential of JAK2 inhibitors. Hematology Am Soc Hematol Educ Program 636–642. Volume: 2009

    Google Scholar 

  39. Pardanani A, Hood J, Lasho T, Levine RL, Martin MB, Noronha G, Finke C, Mak CC, Mesa R, Zhu H, Soll R, Gilliland DG, Tefferi A (2007) TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia 21:1658–1668

    Article  PubMed  CAS  Google Scholar 

  40. Gozgit JM, Bebernitz G, Patil P, Ye M, Parmentier J, Wu J, Su N, Wang T, Ioannidis S, Davies A, Huszar D, Zinda M (2008) 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 283:32334–32343

    Article  PubMed  CAS  Google Scholar 

  41. Ledeboer MW, Pierce AC, Duffy JP, Gao H, Messersmith D, Salituro FG, Nanthakumar S, Come J, Zuccola HJ, Swenson L, Shlyakter D, Mahajan S, Hoock T, Fan B, Tsai WJ, Kolaczkowski E, Carrier S, Hogan JK, Zessis R, Pazhanisamy S, Bennani YL (2009) 2-Aminopyrazolo(1,5-a)pyrimidines as potent and selective inhibitors of JAK2. Bioorg Med Chem Lett 19:6529–6533

    Article  PubMed  CAS  Google Scholar 

  42. Wang T, Duffy JP, Wang J, Halas S, Salituro FG, Pierce AC, Zuccola HJ, Black JR, Hogan JK, Jepson S, Shlyakter D, Mahajan S, Gu Y, Hoock T, Wood M, Furey BF, Frantz JD, Dauffenbach LM, Germann UA, Fan B, Namchuk M, Bennani YL, Ledeboer MW (2009) Janus kinase 2 inhibitors. Synthesis and characterization of a novel polycyclic azaindole. J Med Chem 52:7938–7941

    Article  PubMed  CAS  Google Scholar 

  43. Lim J, Taoka B, Otte RD, Spencer K, Dinsmore CJ, Altman MD, Chan G, Rosenstein C, Sharma S, Su HP, Szewczak AA, Xu L, Yin H, Zugay-Murphy J, Marshall CG, Young JR (2011) Discovery of 1-amino-5 h-pyrido(4,3-b)indol-4-carboxamide inhibitors of Janus kinase 2 (JAK2) for the treatment of myeloproliferative disorders. J Med Chem. 54:7334–7349

    Google Scholar 

  44. Russell SM, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, Migone TS, Noguchi M, Markert ML, Buckley RH, O’Shea JJ, Leonard WJ (1995) Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science 270:797–800

    Article  PubMed  CAS  Google Scholar 

  45. Jiang JK, Ghoreschi K, Deflorian F, Chen Z, Perreira M, Pesu M, Smith J, Nguyen DT, Liu EH, Leister W, Costanzi S, O’Shea JJ, Thomas CJ (2008) Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7 H-pyrrolo(2,3-d)pyrimidin-4-yl)amino)piperi din-1-yl)-3-oxopropanenitrile (CP-690,550). J Med Chem 51:8012–8018

    Article  PubMed  CAS  Google Scholar 

  46. Thoma G, Nuninger F, Falchetto R, Hermes E, Tavares GA, Vangrevelinghe E, Zerwes HG (2011) Identification of a potent Janus kinase 3 inhibitor with high selectivity within the Janus kinase family. J Med Chem 54:284–288

    Article  PubMed  CAS  Google Scholar 

  47. McGovern SL, Caselli E, Grigorieff N, Shoichet BK (2002) A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J Med Chem 45:1712–1722

    Article  PubMed  CAS  Google Scholar 

  48. McGovern SL, Helfand BT, Feng B, Shoichet BK (2003) A specific mechanism of nonspecific inhibition. J Med Chem 46:4265–4272

    Article  PubMed  CAS  Google Scholar 

  49. Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL, Heathcote M, Maman S, Matthews JE, McMenamin RL, Navarro EF, O’Brien MA, O’Reilly M, Rees DC, Reule M, Tisi D, Williams G, Vinkovic M, Wyatt PG (2009) Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J Med Chem 52:379–388

    Article  PubMed  CAS  Google Scholar 

  50. Hedvat M, Huszar D, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, Buettner R, Proia D, Kowolik CM, Xin H, Armstrong B, Bebernitz G, Weng S, Wang L, Ye M, McEachern K, Chen H, Morosini D, Bell K, Alimzhanov M, Ioannidis S, McCoon P, Cao ZA, Yu H, Jove R, Zinda M (2009) The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell 16:487–497

    Article  PubMed  CAS  Google Scholar 

  51. Zarrinkar PP, Gunawardane RN, Cramer MD, Gardner MF, Brigham D, Belli B, Karaman MW, Pratz KW, Pallares G, Chao Q, Sprankle KG, Patel HK, Levis M, Armstrong RC, James J, Bhagwat SS (2009) AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood 114:2984–2992

    Article  PubMed  CAS  Google Scholar 

  52. Hexner EO, Serdikoff C, Jan M, Swider CR, Robinson C, Yang S, Angeles T, Emerson SG, Carroll M, Ruggeri B, Dobrzanski P (2008) Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 111:5663–5671

    Article  PubMed  CAS  Google Scholar 

  53. Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A (2009) 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 23:1441–1445

    Article  PubMed  CAS  Google Scholar 

  54. Li J, Favata M, Kelley JA, Caulder E, Thomas B, Wen X, Sparks RB, Arvanitis A, Rogers JD, Combs AP, Vaddi K, Solomon KA, Scherle PA, Newton R, Fridman JS (2010) INCB16562, a JAK1/2 selective inhibitor, is efficacious against multiple myeloma cells and reverses the protective effects of cytokine and stromal cell support. Neoplasia 12:28–38

    PubMed  CAS  Google Scholar 

  55. Quintas-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, Caulder E, Wen X, Li Y, Waeltz P, Rupar M, Burn T, Lo Y, Kelley J, Covington M, Shepard S, Rodgers JD, Haley P, Kantarjian H, Fridman JS, Verstovsek S (2010) Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 115:3109–3117

    Article  PubMed  CAS  Google Scholar 

  56. Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE, Gozo M, McDowell EP, Levine RL, Doukas J, Mak CC, Noronha G, Martin M, Ko YD, Lee BH, Soll RM, Tefferi A, Hood JD, Gilliland DG (2008) Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell 13:311–320

    Article  PubMed  CAS  Google Scholar 

  57. Shide K, Kameda T, Markovtsov V, Shimoda HK, Tonkin E, Fang S, Liu C, Gelman M, Lang W, Romero J, McLaughlin J, Bhamidipati S, Clough J, Low C, Reitsma A, Siu S, Pine P, Park G, Torneros A, Duan M, Singh R, Payan DG, Matsunaga T, Hitoshi Y, Shimoda K (2011) R723, a selective JAK2 inhibitor, effectively treats JAK2V617F-induced murine myeloproliferative neoplasm. Blood 117:6866–6875

    Article  PubMed  CAS  Google Scholar 

  58. William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET, Goh KC, Ong WC, Goh SK, Hart S, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW (2011) Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1. 1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem 54:4638–4658

    Article  PubMed  CAS  Google Scholar 

  59. Fabian MA, Biggs WH 3rd, Treiber DK, Atteridge CE, Azimioara MD, Benedetti MG, Carter TA, Ciceri P, Edeen PT, Floyd M, Ford JM, Galvin M, Gerlach JL, Grotzfeld RM, Herrgard S, Insko DE, Insko MA, Lai AG, Lelias JM, Mehta SA, Milanov ZV, Velasco AM, Wodicka LM, Patel HK, Zarrinkar PP, Lockhart DJ (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 23:329–336

    Article  PubMed  CAS  Google Scholar 

  60. Lin TH, Hegen M, Quadros E, Nickerson-Nutter CL, Appell KC, Cole AG, Shao Y, Tam S, Ohlmeyer M, Wang B, Goodwin DG, Kimble EF, Quintero J, Gao M, Symanowicz P, Wrocklage C, Lussier J, Schelling SH, Hewet AG, Xuan D, Krykbaev R, Togias J, Xu X, Harrison R, Mansour T, Collins M, Clark JD, Webb ML, Seidl KJ (2010) Selective functional inhibition of JAK-3 is sufficient for efficacy in collagen-induced arthritis in mice. Arthritis Rheum 62:2283–2293

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemical Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

    Christopher J. Burns & David Segal

  2. University of Melbourne, Parkville, VIC, Australia

    Christopher J. Burns & David Segal

  3. SYNthesis medchem, Parkville, Victoria, Australia

    Andrew F. Wilks

Authors
  1. Christopher J. Burns
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Segal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew F. Wilks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew F. Wilks .

Editor information

Editors and Affiliations

  1. Walter and Eliza Hall Institute, Royal Parade 1G, Parkville, 3050, Victoria, Australia

    Sandra E. Nicholson

  2. Walter and Eliza Hall Institute, Royal Parade 1G, Parkville, 3050, Victoria, Australia

    Nicos A. Nicola

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this protocol

Cite this protocol

Burns, C.J., Segal, D., Wilks, A.F. (2013). The Use of JAK-Specific Inhibitors as Chemical Biology Tools. In: Nicholson, S., Nicola, N. (eds) JAK-STAT Signalling. Methods in Molecular Biology, vol 967. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-242-1_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-242-1_7

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-241-4

  • Online ISBN: 978-1-62703-242-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation