Ibrutinib and novel BTK inhibitors in clinical development

Journal of Hematology and Oncology

Volumn 6, Issue 1, 2013, Pages

  Akinleye, Akintunde ^a   Chen, Yamei ^a,b   Mukhi, Nikhil ^a   Song, Yongping ^c   Liu, Delong ^a,c  

^a NEW YORK MEDICAL COLLEGE   (United States)

^b XIAMEN UNIVERSITY   (China)

^c ZHENGZHOU UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

2 CYANO N (2,5 DIBROMOPHENYL) 3 HYDROXYCROTONAMIDE; ACY 1215; BENDAMUSTINE; BRUTON TYROSINE KINASE; BRUTON TYROSINE KINASE INHIBITOR; CC 292; CGI 1746; CGI 560; CNX 774; GDC 0834; HM 71224; IBRUTINIB; INTERLEUKIN 6; INTERLEUKIN 8; OFATUMUMAB; ONO 4059; RITUXIMAB; RN 486; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANEMIA; ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; AUTOIMMUNE DISEASE; B CELL LEUKEMIA; B CELL LYMPHOMA; B LYMPHOCYTE; CARCINOGENESIS; CELL DIFFERENTIATION; CELL MOTILITY; CELL SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL EFFECTIVENESS; CLINICAL FEATURE; CONSTIPATION; CYTOKINE PRODUCTION; DIARRHEA; DISEASE COURSE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SAFETY; FATIGUE; FOLLOW UP; HEADACHE; HUMAN; IC 50; LARGE CELL LYMPHOMA; LUPUS ERYTHEMATOSUS NEPHRITIS; LYMPHOCYTOSIS; LYMPHOPOIESIS; MANTLE CELL LYMPHOMA; MAXIMUM PLASMA CONCENTRATION; MONOCYTE; MULTIPLE MYELOMA; MUSCLE SPASM; MYALGIA; NAUSEA; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; RASH; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; THERAPY EFFECT; THROMBOCYTOPENIA; TREATMENT RESPONSE; XEROSTOMIA;

ANIMALS; CLINICAL TRIALS, PHASE III AS TOPIC; HUMANS; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PYRAZOLES; PYRIMIDINES; SIGNAL TRANSDUCTION;

EID: 84883160397     PISSN: None     EISSN: 17568722     Source Type: Journal    
DOI: 10.1186/1756-8722-6-59     Document Type: Review

References (85)

1. Novel targeted agents for gastric cancer. Liu L, Wu N, Li J, J Hematol Oncol 2012 5 1 31 10.1186/1756-8722-5-31 22709792
2. Recent advances and novel agents for gastrointestinal stromal tumor (GIST). Lamba G, Ambrale S, Lee B, Gupta R, Rafiyath S, Liu D, J Hematol Oncol 2012 5 1 21 10.1186/1756-8722-5-21 22569033
3. Current management and novel agents for malignant melanoma. Lee B, Mukhi N, Liu D, J Hematol Oncol 2012 5 1 3 10.1186/1756-8722-5-3 22333219
4. Polo-like kinase 1 as target for cancer therapy. WeiSZ L, Efferth T, Exp J Hematol Oncol 2012 1 1 38 10.1186/2162-3619-1-38
5. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, et al. J Clin Oncol 1998 16 8 2825 2833 9704735
6. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haioun C, Foussard C, Sebban C, et al. Blood 2001 97 1 101 106 10.1182/blood.V97.1.101 11133748
7. Novel CD20 monoclonal antibodies for lymphoma therapy. Cang S, Mukhi N, Wang K, Liu D, J Hematol Oncol 2012 5 64 10.1186/1756-8722-5-64 23057966
8. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Wang K, Wei G, Liu D, Exp J Hematol Oncol 2012 1 1 36 10.1186/2162-3619-1-36
9. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, Flynn J, Jones J, Blum KA, Buggy JJ, et al. Blood 2011 117 23 6287 6296 10.1182/blood-2011-01-328484 21422473
10. Mechanisms of B-cell lymphoma pathogenesis. Kuppers R, Nat Rev Cancer 2005 5 4 251 262 10.1038/nrc1589 15803153
11. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, Miller RA, et al. Proc Natl Acad Sci U S A 2010 107 29 13075 13080 10.1073/pnas.1004594107 20615965
12. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, Sparkes RS, Kubagawa H, Mohandas T, Quan S, et al. Cell 1993 72 2 279 290 10.1016/0092-8674(93)90667-F 8425221
13. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, Hammarstrom L, Kinnon C, Levinsky R, Bobrow M, et al. Nature 1993 361 6409 226 233 10.1038/361226a0 8380905
14. The Bruton's tyrosine kinase gene is expressed throughout B cell differentiation, from early precursor B cell stages preceding immunoglobulin gene rearrangement up to mature B cell stages. de Weers M, Verschuren MC, Kraakman ME, Mensink RG, Schuurman RK, van Dongen JJ, Hendriks RW, Eur J Immunol 1993 23 12 3109 3114 10.1002/eji.1830231210 8258324
15. X-linked agammaglobulinemia. Timmers E, de Weers M, Alt FW, Hendriks RW, Schuurman RK, Clin Immunol Immunopathol 1991 61 2 Pt 2 83 S93 1934617
16. Genomic organization of the Btk gene and exon scanning for mutations in patients with X-linked agammaglobulinemia. Hagemann TL, Chen Y, Rosen FS, Kwan SP, Hum Mol Genet 1994 3 10 1743 1749 10.1093/hmg/3.10.1743 7880320
17. Functions of Bruton's tyrosine kinase in mast and B cells. Kawakami Y, Kitaura J, Hata D, Yao L, Kawakami T, J Leukoc Biol 1999 65 3 286 290 10080529
18. Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I. Rajaiya J, Nixon JC, Ayers N, Desgranges ZP, Roy AL, Webb CF, Mol Cell Biol 2006 26 12 4758 4768 10.1128/MCB.02009-05 16738337
19. Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein. Liu W, Quinto I, Chen X, Palmieri C, Rabin RL, Schwartz OM, Nelson DL, Scala G, Nat Immunol 2001 2 10 939 946 10.1038/ni1001-939 11577348
20. Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells. Varnai P, Rother KI, Balla T, J Biol Chem 1999 274 16 10983 10989 10.1074/jbc.274.16.10983 10196179
21. Tec homology (TH) adjacent to the PH domain. Vihinen M, Nilsson L, Smith CI, FEBS letters 1994 350 2-3 263 265 8070576
22. PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization. Kang SW, Wahl MI, Chu J, Kitaura J, Kawakami Y, Kato RM, Tabuchi R, Tarakhovsky A, Kawakami T, Turck CW, et al. EMBO J 2001 20 20 5692 5702 10.1093/emboj/20.20.5692 11598012
23. Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases. Nore BF, Mattsson PT, Antonsson P, Backesjo CM, Westlund A, Lennartsson J, Hansson H, Low P, Ronnstrand L, Smith CI, Biochim Biophys Acta 2003 1645 2 123 132 10.1016/S1570-9639(02)00524-1 12573241
24. Regulation of Btk function by a major autophosphorylation site within the SH3 domain. Park H, Wahl MI, Afar DE, Turck CW, Rawlings DJ, Tam C, Scharenberg AM, Kinet JP, Witte ON, Immunity 1996 4 5 515 525 10.1016/S1074-7613(00)80417-3 8630736
25. Nucleocytoplasmic shuttling of Bruton's tyrosine kinase. Mohamed AJ, Vargas L, Nore BF, Backesjo CM, Christensson B, Smith CI, J Biol Chem 2000 275 51 40614 40619 10.1074/jbc.M006952200 11016936
26. Large-scale proteomics analysis of the human kinome. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H, Mol Cell Proteomics 2009 8 7 1751 1764 10.1074/mcp.M800588-MCP200 19369195
27. Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Mohamed AJ, Yu L, Backesjo CM, Vargas L, Faryal R, Aints A, Christensson B, Berglof A, Vihinen M, Nore BF, et al. Immunol Rev 2009 228 1 58 73 10.1111/j.1600-065X.2008.00741.x 19290921
28. Btk function in B cell development and response. Satterthwaite AB, Li Z, Witte ON, Semin Immunol 1998 10 4 309 316 10.1006/smim.1998.0123 9695187
29. Bruton's tyrosine kinase is required for TLR2 and TLR4-induced TNF, but not IL-6, production. Horwood NJ, Page TH, McDaid JP, Palmer CD, Campbell J, Mahon T, Brennan FM, Webster D, Foxwell BM, J Immunol 2006 176 6 3635 3641 16517732
30. Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells. Sharma S, Orlowski G, Song W, J Immunol 2009 182 1 329 339 19109164
31. BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement. Yang W, Desiderio S, Proc Natl Acad Sci U S A 1997 94 2 604 609 10.1073/pnas.94.2.604 9012831
32. Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme function in B-cell signaling. Rodriguez R, Matsuda M, Perisic O, Bravo J, Paul A, Jones NP, Light Y, Swann K, Williams RL, Katan M, J Biol Chem 2001 276 51 47982 47992 11606584
33. MEK and the inhibitors: from bench to bedside. Akinleye A, Furqan M, Mukhi N, Ravella P, Liu D, J Hematol Oncol 2013 6 1 27 10.1186/1756-8722-6-27 23587417
34. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Furqan M, Mukhi N, Lee B, Liu D, Biomarker Research 2013 1 1 5 10.1186/2050-7771-1-5
35. B-Raf and the inhibitors: from bench to bedside. Huang T, Karsy M, Zhuge J, Zhong M, Liu D, J Hematol Oncol 2013 6 1 30 10.1186/1756-8722-6-30 23617957
36. Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. Doyle SL, Jefferies CA, Feighery C, O'Neill LA, J Biol Chem 2007 282 51 36953 36960 10.1074/jbc.M707682200 17932028
37. Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein. Yamadori T, Baba Y, Matsushita M, Hashimoto S, Kurosaki M, Kurosaki T, Kishimoto T, Tsukada S, Proc Natl Acad Sci U S A 1999 96 11 6341 6346 10.1073/pnas.96.11.6341 10339589
38. Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx. Vargas L, Nore BF, Berglof A, Heinonen JE, Mattsson PT, Smith CI, Mohamed AJ, J Biol Chem 2002 277 11 9351 9357 10.1074/jbc.M108537200 11751885
39. Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1. Yu L, Mohamed AJ, Vargas L, Berglof A, Finn G, Lu KP, Smith CI, J Biol Chem 2006 281 26 18201 18207 10.1074/jbc.M603090200 16644721
40. Bruton's tyrosine kinase (BTK) as a dual-function regulator of apoptosis. Uckun FM, Biochem Pharmacol 1998 56 6 683 691 10.1016/S0006-2952(98)00122-1 9751072
41. Bruton's tyrosine kinase cooperates with the B cell linker protein SLP-65 as a tumor suppressor in Pre-B cells. Kersseboom R, Middendorp S, Dingjan GM, Dahlenborg K, Reth M, Jumaa H, Hendriks RW, J Exp Med 2003 198 1 91 98 10.1084/jem.20030615 12835482
42. Bruton's tyrosine kinase as an inhibitor of the Fas/CD95 death-inducing signaling complex. Vassilev A, Ozer Z, Navara C, Mahajan S, Uckun FM, J Biol Chem 1999 274 3 1646 1656 10.1074/jbc.274.3.1646 9880544
43. Cutting edge: constitutive B cell receptor signaling is critical for basal growth of B lymphoma. Gururajan M, Jennings CD, Bondada S, J Immunol 2006 176 10 5715 5719 16670274
44. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Buggy JJ, Elias L, Int Rev Immunol 2012 31 2 119 132 10.3109/08830185.2012.664797 22449073
45. Bruton's tyrosine kinase mediated signaling enhances leukemogenesis in a mouse model for chronic lymphocytic leukemia. Kil LP, de Bruijn MJ, van Hulst JA, Langerak AW, Yuvaraj S, Hendriks RW, Am J Blood Res 2013 3 1 71 83 23359016
46. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, et al. Nature 2010 463 7277 88 92 10.1038/nature08638 20054396
47. Multiple colorectal neoplasms in X-linked agammaglobulinemia. Brosens LA, Tytgat KM, Morsink FH, Sinke RJ, Ten Berge IJ, Giardiello FM, Offerhaus GJ, Keller JJ, Clin Gastroenterol Hepatol 2008 6 1 115 119 10.1016/j.cgh.2007.08.019 17967562
48. Defective expression of Bruton's tyrosine kinase in acute lymphoblastic leukemia. Goodman PA, Wood CM, Vassilev AO, Mao C, Uckun FM, Leuk Lymphoma 2003 44 6 1011 1018 10.1080/1042819031000067576 12854903
49. Phosphorylation of Bruton's tyrosine kinase by c-Abl. Backesjo CM, Vargas L, Superti-Furga G, Smith CI, Biochem Biophys Res Commun 2002 299 3 510 515 10.1016/S0006-291X(02)02643-8 12445832
50. Emerging drug profiles: Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Burger JA, Buggy JJ, Leuk Lymphoma 2013 54 10.3109/10428194. 10422013.10777837
51. Modulating proximal cell signaling by targeting Btk ameliorates humoral autoimmunity and end-organ disease in murine lupus. Hutcheson J, Vanarsa K, Bashmakov A, Grewal S, Sajitharan D, Chang BY, Buggy JJ, Zhou XJ, Du Y, Satterthwaite AB, et al. Arthritis Res Ther 2012 14 6 243 10.1186/ar4086 23136880
52. More than just B-cell inhibition. Ruderman EM, Pope RM, Arthritis Res Ther 2011 13 4 125 10.1186/ar3439 21878134
53. Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. Pan Z, Scheerens H, Li SJ, Schultz BE, Sprengeler PA, Burrill LC, Mendonca RV, Sweeney MD, Scott KC, Grothaus PG, et al. ChemMedChem 2007 2 1 58 61 10.1002/cmdc.200600221 17154430
54. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O'Brien S, Chiorazzi N, Burger JA, Blood 2012 119 5 1182 1189 10.1182/blood-2011-10-386417 22180443
55. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. de Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M, Blood 2012 119 11 2590 2594 10.1182/blood-2011-11-390989 22279054
56. Activity of Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) in B-Cell Acute Lymphoblastic Leukemia (B-ALL). Kim E, et al. Proc ASH 2012 Abstr. 2569
57. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, et al. J Clin Oncol 2013 31 1 88 94 10.1200/JCO.2012.42. 7906 23045577
58. Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma. Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, et al. N Engl J Med 2013 369 6 507 516 10.1056/NEJMoa1306220 23782157
59. The Bruton's Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Is Active and Tolerated in Relapsed Follicular Lymphoma. Kunkel L, et al. Proc ASH 2012 2012 Abst. 156
60. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, et al. N Engl J Med 2013 369 1 32 42 10.1056/NEJMoa1215637 23782158
61. The Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Promotes High Response Rate, Durable Remissions, and Is Tolerable in Treatment Naïve (TN) and Relapsed or Refractory (RR) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Patients Including Patients with High-Risk (HR) Disease: New and Updated Results of 116 Patients in a Phase Ib/II Study. Byrd J, et al. Proc ASH 2012 abst. 189
62. Therapeutic advancement of chronic lymphocytic leukemia. Lu K, Wang X, J Hematol Oncol 2012 5 1 55 10.1186/1756-8722-5-55 22980425
63. The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study. Wilson W, et al. Proc ASH 2012 Abstr. 686
64. Early Changes in Cytokines, Chemokines and Indices of Bone Metabolism in a Phase 2 Study of the Bruton Tyrosine Kinase (Btk) Inhibitor, Ibrutinib (PCI-32765) in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM). Vij R, et al. Proc ASH 2012 Abstr. 4039
65. Combination of ACY1215, a Selective Histone Deacetylase 6 (HDAC6) Inhibitor with the Bruton Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Represents a Novel Therapeutic Strategy in Mantle Cell Lymphoma (MCL). Sahakian E, et al. Proc ASH 2012 Abst. 1660
66. The Btk Inhibitor Ibrutinib (PCI-32765) in Combination with Rituximab Is Well Tolerated and Displays Profound Activity in High-Risk Chronic Lymphocytic Leukemia (CLL) Patients. Burger J, Wierda W, Hoellenriegel J, et al. Proc ASH Abst.187
67. Combination of the Bruton's tyrosine kinase inhibitor PCI-32765 with bendamustine/rituximab (BR) in patients with relapsed/refractory chronic lymphocytic leukemia: Interim results of a phase Ib/II study. Brown J, et al. EHA Meeting 2012 Abstr. 1590
68. A phase Ib/II study evaluating activity and tolerability of BTK inhibitor PCI-32765 and ofatumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases. Jaglowski S, et al. J Clin Oncol 2012 Abstr. 6508
69. A Phase I Trial of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in Combination with Rituximab (R) and Bendamustine in Patients with Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL). Blum K, et al. Proc ASH 2012 Abstr. 1643
70. Antiarthritis effect of a novel Bruton's tyrosine kinase (BTK) inhibitor in rat collagen-induced arthritis and mechanism-based pharmacokinetic/ pharmacodynamic modeling: relationships between inhibition of BTK phosphorylation and efficacy. Liu L, Di Paolo J, Barbosa J, Rong H, Reif K, Wong H, J Pharmacol Exp Ther 2011 338 1 154 163 10.1124/jpet.111.181545 21521773
71. Significant species difference in amide hydrolysis of GDC-0834, a novel potent and selective Bruton's tyrosine kinase inhibitor. Liu L, Halladay JS, Shin Y, Wong S, Coraggio M, La H, Baumgardner M, Le H, Gopaul S, Boggs J, et al. Drug Metab Dispos 2011 39 10 1840 1849 10.1124/dmd.111.040840 21742900
72. RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. Xu D, Kim Y, Postelnek J, Vu MD, Hu DQ, Liao C, Bradshaw M, Hsu J, Zhang J, Pashine A, et al. J Pharmacol Exp Ther 2012 341 1 90 103 10.1124/jpet.111.187740 22228807
73. Suppression of glomerulonephritis in lupus prone NZB/W mice by RN486, a selective inhibitor of Bruton's Tyrosine Kinase. Mina-Osorio P, Lastant J, Keirstead N, Whittard T, Ayala J, Stefanova S, Garrido R, Dimaano N, Hilton H, Giron M, et al. Arthritis Rheum 2013 10.1002/art.38047
74. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, Carano RA, Darrow J, Davies DR, DeForge LE, et al. Nat Chem Biol 2011 7 1 41 50 21113169
75. Bodiam S, et al. THE ONES TO WATCH: A PHARMA MATTERS REPORT THOMSON REUTERS 2013
76. Inhibition of Btk with CC-292 Provides Early Pharmacodynamic Assessment of Activity in Mice and Humans. Evans EK, Tester R, Aslanian S, Karp R, Sheets M, Labenski MT, Witowski SR, Lounsbury H, Chaturvedi P, Mazdiyasni H, et al. J Pharmacol Exp Ther 2013 346 Epub 10.1124/jpet.1113.203489
77. CC-292, A Novel Bruton's Tyrosine Kinase Inhibitor Alone And In Combination With Carfilzomib Impacts Bone Resorption In Multiple Myeloma By Blocking Osteoclast Sealing Zone Formation. Homare E, et al. EHA 2013 Congress 2013 abstr.S543
78. Phase 1 Study of single agent CC-292, a highly selective Bruton's Tyrosine Kinase (BTK) inhibitor, in relapsed/refractory Chronic Lymphocytic Leukemia (CLL) and B-Cell Non-Hodgkin Lymphoma (B-NHL). Brown J, et al. EHA 2013 Congress 2013 Abstr. 3793
79. Development of a Bruton's Tyrosine Kinase (Btk) Inhibitor, ONO-4059: Efficacy in a Collagen Induced Arthritis (CIA) Model Indicates Potential Treatment for Rheumatoid Arthritis (RA). Yoshizawa T, et al. Arthritis and rheumatism 2012 64 Suppl 10 1660
80. In vitro reactivity assessment of covalent drugs targeting Bruton's tyrosine kinase. Labenski M, et al. 17th North Am Meet Int Soc Study Xenobiot (ISSX) 2011 Abst. P211
81. In vivo pharmacokinetic features, toxicity profile, and chemosensitizing activity of alpha-cyano-beta-hydroxy-beta- methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13), a novel antileukemic agent targeting Bruton's tyrosine kinase. Uckun FM, Zheng Y, Cetkovic-Cvrlje M, Vassilev A, Lisowski E, Waurzyniak B, Chen H, Carpenter R, Chen CL, Clin Cancer Res 2002 8 5 1224 1233 12006542
82. Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Uckun FM, Dibirdik I, Qazi S, Vassilev A, Ma H, Mao C, Benyumov A, Emami KH, Bioorg Med Chem 2007 15 2 800 814 10.1016/j.bmc.2006.10.050 17098432
83. Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N- (2, 5-dibromophenyl)propenamide]. Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, Uckun FM, J Biol Chem 1999 274 14 9587 9599 10.1074/jbc.274.14.9587 10092645
84. Role of Bruton's tyrosine kinase in myeloma cell migration and induction of bone disease. Bam R, Ling W, Khan S, Pennisi A, Venkateshaiah SU, Li X, van Rhee F, Usmani S, Barlogie B, Shaughnessy J, et al. Am J Hematol 2013 88 6 463 471 10.1002/ajh.23433 23456977
85. BRAF inhibitors: research accelerates in wake of positive findings. Brower V, J Natl Cancer Inst 2010 102 4 214 215 10.1093/jnci/djq037 20145213