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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2013

Open Access 01-12-2013 | Review

Ibrutinib and novel BTK inhibitors in clinical development

Authors: Akintunde Akinleye, Yamei Chen, Nikhil Mukhi, Yongping Song, Delong Liu

Published in: Journal of Hematology & Oncology | Issue 1/2013

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Abstract

Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton’s tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials. However, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to benefit from BTK inhibition. This review summarizes preclinical and clinical development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI-1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B-cell malignancies and autoimmune disorders.
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Literature
1.
2.
Lamba G, Ambrale S, Lee B, Gupta R, Rafiyath S, Liu D: Recent advances and novel agents for gastrointestinal stromal tumor (GIST). J Hematol Oncol. 2012, 5 (1): 21-10.1186/1756-8722-5-21.PubMedCentralCrossRefPubMed
3.
4.
WeiSZ L, Efferth T: Polo-like kinase 1 as target for cancer therapy. Exp J Hematol Oncol. 2012, 1 (1): 38-10.1186/2162-3619-1-38.CrossRef
5.
McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F: Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998, 16 (8): 2825-2833.PubMed
6.
Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haioun C, Foussard C, Sebban C: Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001, 97 (1): 101-106. 10.1182/blood.V97.1.101.CrossRefPubMed
7.
8.
Wang K, Wei G, Liu D: CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Exp J Hematol Oncol. 2012, 1 (1): 36-10.1186/2162-3619-1-36.CrossRef
9.
Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, Flynn J, Jones J, Blum KA, Buggy JJ: Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011, 117 (23): 6287-6296. 10.1182/blood-2011-01-328484.PubMedCentralCrossRefPubMed
10.
Kuppers R: Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer. 2005, 5 (4): 251-262. 10.1038/nrc1589.CrossRefPubMed
11.
Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, Miller RA: The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010, 107 (29): 13075-13080. 10.1073/pnas.1004594107.PubMedCentralCrossRefPubMed
12.
Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, Sparkes RS, Kubagawa H, Mohandas T, Quan S: Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 1993, 72 (2): 279-290. 10.1016/0092-8674(93)90667-F.CrossRefPubMed
13.
Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, Hammarstrom L, Kinnon C, Levinsky R, Bobrow M: The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993, 361 (6409): 226-233. 10.1038/361226a0.CrossRefPubMed
14.
de Weers M, Verschuren MC, Kraakman ME, Mensink RG, Schuurman RK, van Dongen JJ, Hendriks RW: 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. Eur J Immunol. 1993, 23 (12): 3109-3114. 10.1002/eji.1830231210.CrossRefPubMed
15.
Timmers E, de Weers M, Alt FW, Hendriks RW, Schuurman RK: X-linked agammaglobulinemia. Clin Immunol Immunopathol. 1991, 61 (2 Pt 2): S83-S93.CrossRefPubMed
16.
Hagemann TL, Chen Y, Rosen FS, Kwan SP: Genomic organization of the Btk gene and exon scanning for mutations in patients with X-linked agammaglobulinemia. Hum Mol Genet. 1994, 3 (10): 1743-1749. 10.1093/hmg/3.10.1743.CrossRefPubMed
17.
Kawakami Y, Kitaura J, Hata D, Yao L, Kawakami T: Functions of Bruton’s tyrosine kinase in mast and B cells. J Leukoc Biol. 1999, 65 (3): 286-290.PubMed
18.
Rajaiya J, Nixon JC, Ayers N, Desgranges ZP, Roy AL, Webb CF: Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I. Mol Cell Biol. 2006, 26 (12): 4758-4768. 10.1128/MCB.02009-05.PubMedCentralCrossRefPubMed
19.
Liu W, Quinto I, Chen X, Palmieri C, Rabin RL, Schwartz OM, Nelson DL, Scala G: Direct inhibition of Bruton’s tyrosine kinase by IBtk, a Btk-binding protein. Nat Immunol. 2001, 2 (10): 939-946. 10.1038/ni1001-939.CrossRefPubMed
20.
Varnai P, Rother KI, Balla T: Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton’s tyrosine kinase pleckstrin homology domain visualized in single living cells. J Biol Chem. 1999, 274 (16): 10983-10989. 10.1074/jbc.274.16.10983.CrossRefPubMed
21.
Vihinen M, Nilsson L, Smith CI: Tec homology (TH) adjacent to the PH domain. FEBS letters. 1994, 350 (2–3): 263-265.CrossRefPubMed
22.
Kang SW, Wahl MI, Chu J, Kitaura J, Kawakami Y, Kato RM, Tabuchi R, Tarakhovsky A, Kawakami T, Turck CW: PKCbeta modulates antigen receptor signaling via regulation of Btk membrane localization. EMBO J. 2001, 20 (20): 5692-5702. 10.1093/emboj/20.20.5692.PubMedCentralCrossRefPubMed
23.
Nore BF, Mattsson PT, Antonsson P, Backesjo CM, Westlund A, Lennartsson J, Hansson H, Low P, Ronnstrand L, Smith CI: Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases. Biochim Biophys Acta. 2003, 1645 (2): 123-132. 10.1016/S1570-9639(02)00524-1.CrossRefPubMed
24.
Park H, Wahl MI, Afar DE, Turck CW, Rawlings DJ, Tam C, Scharenberg AM, Kinet JP, Witte ON: Regulation of Btk function by a major autophosphorylation site within the SH3 domain. Immunity. 1996, 4 (5): 515-525. 10.1016/S1074-7613(00)80417-3.CrossRefPubMed
25.
Mohamed AJ, Vargas L, Nore BF, Backesjo CM, Christensson B, Smith CI: Nucleocytoplasmic shuttling of Bruton’s tyrosine kinase. J Biol Chem. 2000, 275 (51): 40614-40619. 10.1074/jbc.M006952200.CrossRefPubMed
26.
Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009, 8 (7): 1751-1764. 10.1074/mcp.M800588-MCP200.PubMedCentralCrossRefPubMed
27.
Mohamed AJ, Yu L, Backesjo CM, Vargas L, Faryal R, Aints A, Christensson B, Berglof A, Vihinen M, Nore BF: Bruton’s tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. 2009, 228 (1): 58-73. 10.1111/j.1600-065X.2008.00741.x.CrossRefPubMed
28.
Satterthwaite AB, Li Z, Witte ON: Btk function in B cell development and response. Semin Immunol. 1998, 10 (4): 309-316. 10.1006/smim.1998.0123.CrossRefPubMed
29.
Horwood NJ, Page TH, McDaid JP, Palmer CD, Campbell J, Mahon T, Brennan FM, Webster D, Foxwell BM: Bruton’s tyrosine kinase is required for TLR2 and TLR4-induced TNF, but not IL-6, production. J Immunol. 2006, 176 (6): 3635-3641.CrossRefPubMed
30.
Sharma S, Orlowski G, Song W: Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells. J Immunol. 2009, 182 (1): 329-339.PubMedCentralCrossRefPubMed
31.
Yang W, Desiderio S: BAP-135, a target for Bruton’s tyrosine kinase in response to B cell receptor engagement. Proc Natl Acad Sci U S A. 1997, 94 (2): 604-609. 10.1073/pnas.94.2.604.PubMedCentralCrossRefPubMed
32.
Rodriguez R, Matsuda M, Perisic O, Bravo J, Paul A, Jones NP, Light Y, Swann K, Williams RL, Katan M: Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme function in B-cell signaling. J Biol Chem. 2001, 276 (51): 47982-47992.PubMed
33.
Akinleye A, Furqan M, Mukhi N, Ravella P, Liu D: MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013, 6 (1): 27-10.1186/1756-8722-6-27.PubMedCentralCrossRefPubMed
34.
Furqan M, Mukhi N, Lee B, Liu D: Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomarker Research. 2013, 1 (1): 5-10.1186/2050-7771-1-5.PubMedCentralCrossRefPubMed
35.
36.
Doyle SL, Jefferies CA, Feighery C, O’Neill LA: Signaling by Toll-like receptors 8 and 9 requires Bruton’s tyrosine kinase. J Biol Chem. 2007, 282 (51): 36953-36960. 10.1074/jbc.M707682200.CrossRefPubMed
37.
Yamadori T, Baba Y, Matsushita M, Hashimoto S, Kurosaki M, Kurosaki T, Kishimoto T, Tsukada S: Bruton’s tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein. Proc Natl Acad Sci U S A. 1999, 96 (11): 6341-6346. 10.1073/pnas.96.11.6341.PubMedCentralCrossRefPubMed
38.
Vargas L, Nore BF, Berglof A, Heinonen JE, Mattsson PT, Smith CI, Mohamed AJ: Functional interaction of caveolin-1 with Bruton’s tyrosine kinase and Bmx. J Biol Chem. 2002, 277 (11): 9351-9357. 10.1074/jbc.M108537200.CrossRefPubMed
39.
Yu L, Mohamed AJ, Vargas L, Berglof A, Finn G, Lu KP, Smith CI: Regulation of Bruton tyrosine kinase by the peptidylprolyl isomerase Pin1. J Biol Chem. 2006, 281 (26): 18201-18207. 10.1074/jbc.M603090200.CrossRefPubMed
40.
Uckun FM: Bruton’s tyrosine kinase (BTK) as a dual-function regulator of apoptosis. Biochem Pharmacol. 1998, 56 (6): 683-691. 10.1016/S0006-2952(98)00122-1.CrossRefPubMed
41.
Kersseboom R, Middendorp S, Dingjan GM, Dahlenborg K, Reth M, Jumaa H, Hendriks RW: Bruton’s tyrosine kinase cooperates with the B cell linker protein SLP-65 as a tumor suppressor in Pre-B cells. J Exp Med. 2003, 198 (1): 91-98. 10.1084/jem.20030615.PubMedCentralCrossRefPubMed
42.
Vassilev A, Ozer Z, Navara C, Mahajan S, Uckun FM: Bruton’s tyrosine kinase as an inhibitor of the Fas/CD95 death-inducing signaling complex. J Biol Chem. 1999, 274 (3): 1646-1656. 10.1074/jbc.274.3.1646.CrossRefPubMed
43.
Gururajan M, Jennings CD, Bondada S: Cutting edge: constitutive B cell receptor signaling is critical for basal growth of B lymphoma. J Immunol. 2006, 176 (10): 5715-5719.CrossRefPubMed
44.
Buggy JJ, Elias L: Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol. 2012, 31 (2): 119-132. 10.3109/08830185.2012.664797.CrossRefPubMed
45.
Kil LP, de Bruijn MJ, van Hulst JA, Langerak AW, Yuvaraj S, Hendriks RW: Bruton’s tyrosine kinase mediated signaling enhances leukemogenesis in a mouse model for chronic lymphocytic leukemia. Am J Blood Res. 2013, 3 (1): 71-83.PubMedCentralPubMed
46.
Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y: Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010, 463 (7277): 88-92. 10.1038/nature08638.PubMedCentralCrossRefPubMed
47.
Brosens LA, Tytgat KM, Morsink FH, Sinke RJ, Ten Berge IJ, Giardiello FM, Offerhaus GJ, Keller JJ: Multiple colorectal neoplasms in X-linked agammaglobulinemia. Clin Gastroenterol Hepatol. 2008, 6 (1): 115-119. 10.1016/j.cgh.2007.08.019.CrossRefPubMed
48.
Goodman PA, Wood CM, Vassilev AO, Mao C, Uckun FM: Defective expression of Bruton’s tyrosine kinase in acute lymphoblastic leukemia. Leuk Lymphoma. 2003, 44 (6): 1011-1018. 10.1080/1042819031000067576.CrossRefPubMed
49.
Backesjo CM, Vargas L, Superti-Furga G, Smith CI: Phosphorylation of Bruton’s tyrosine kinase by c-Abl. Biochem Biophys Res Commun. 2002, 299 (3): 510-515. 10.1016/S0006-291X(02)02643-8.CrossRefPubMed
50.
Burger JA, Buggy JJ: Emerging drug profiles: Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Leuk Lymphoma. 2013, 54: 10.3109/10428194.10422013.10777837.
51.
Hutcheson J, Vanarsa K, Bashmakov A, Grewal S, Sajitharan D, Chang BY, Buggy JJ, Zhou XJ, Du Y, Satterthwaite AB: Modulating proximal cell signaling by targeting Btk ameliorates humoral autoimmunity and end-organ disease in murine lupus. Arthritis Res Ther. 2012, 14 (6): R243-10.1186/ar4086.PubMedCentralCrossRefPubMed
52.
53.
Pan Z, Scheerens H, Li SJ, Schultz BE, Sprengeler PA, Burrill LC, Mendonca RV, Sweeney MD, Scott KC, Grothaus PG: Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase. ChemMedChem. 2007, 2 (1): 58-61. 10.1002/cmdc.200600221.CrossRefPubMed
54.
Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O’Brien S, Chiorazzi N, Burger JA: The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012, 119 (5): 1182-1189. 10.1182/blood-2011-10-386417.CrossRefPubMed
55.
de Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M: The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012, 119 (11): 2590-2594. 10.1182/blood-2011-11-390989.CrossRefPubMed
56.
Kim E: Activity of Bruton’s Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) in B-Cell Acute Lymphoblastic Leukemia (B-ALL). Proc ASH. 2012, Abstr. 2569
57.
Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY: Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013, 31 (1): 88-94. 10.1200/JCO.2012.42.7906.CrossRefPubMed
58.
Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME: Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2013, 369 (6): 507-516. 10.1056/NEJMoa1306220.PubMedCentralCrossRefPubMed
59.
Kunkel L: The Bruton’s Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Is Active and Tolerated in Relapsed Follicular Lymphoma. Proc ASH. 2012, 2012-Abst. 156
60.
Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG: Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013, 369 (1): 32-42. 10.1056/NEJMoa1215637.PubMedCentralCrossRefPubMed
61.
Byrd J: 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. Proc ASH. 2012, abst. 189
62.
63.
Wilson W: 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. Proc ASH. 2012, Abstr. 686
64.
Vij R: 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). Proc ASH. 2012, Abstr. 4039
65.
Sahakian E: 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). Proc ASH. 2012, Abst. 1660
66.
Burger J, Wierda W, Hoellenriegel J: 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. Proc ASH. Abst.187
67.
Brown J: 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. EHA Meeting. 2012, Abstr. 1590
68.
Jaglowski S: 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. J Clin Oncol. 2012, Abstr. 6508
69.
Blum K: 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). Proc ASH. 2012, Abstr. 1643
70.
Liu L, Di Paolo J, Barbosa J, Rong H, Reif K, Wong H: 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. J Pharmacol Exp Ther. 2011, 338 (1): 154-163. 10.1124/jpet.111.181545.CrossRefPubMed
71.
Liu L, Halladay JS, Shin Y, Wong S, Coraggio M, La H, Baumgardner M, Le H, Gopaul S, Boggs J: Significant species difference in amide hydrolysis of GDC-0834, a novel potent and selective Bruton’s tyrosine kinase inhibitor. Drug Metab Dispos. 2011, 39 (10): 1840-1849. 10.1124/dmd.111.040840.CrossRefPubMed
72.
Xu D, Kim Y, Postelnek J, Vu MD, Hu DQ, Liao C, Bradshaw M, Hsu J, Zhang J, Pashine A: RN486, a selective Bruton’s tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012, 341 (1): 90-103. 10.1124/jpet.111.187740.CrossRefPubMed
73.
Mina-Osorio P, Lastant J, Keirstead N, Whittard T, Ayala J, Stefanova S, Garrido R, Dimaano N, Hilton H, Giron M: Suppression of glomerulonephritis in lupus prone NZB/W mice by RN486, a selective inhibitor of Bruton’s Tyrosine Kinase. Arthritis Rheum. 2013, 10.1002/art.38047.
74.
Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, Carano RA, Darrow J, Davies DR, DeForge LE: Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol. 2011, 7 (1): 41-50.CrossRefPubMed
75.
Bodiam S: THE ONES TO WATCH: A PHARMA MATTERS REPORT. 2013, THOMSON REUTERS
76.
Evans EK, Tester R, Aslanian S, Karp R, Sheets M, Labenski MT, Witowski SR, Lounsbury H, Chaturvedi P, Mazdiyasni H: Inhibition of Btk with CC-292 Provides Early Pharmacodynamic Assessment of Activity in Mice and Humans. J Pharmacol Exp Ther. 2013, 346: 10.1124/jpet.1113.203489. Epub
77.
Homare E: 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. EHA 2013 Congress. 2013, abstr.S543
78.
Brown J: 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). EHA 2013 Congress. 2013, Abstr. 3793
79.
Yoshizawa T: 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). Arthritis and rheumatism. 2012, 64 Suppl 10: 1660-
80.
Labenski M: In vitro reactivity assessment of covalent drugs targeting Bruton’s tyrosine kinase. 17th North Am Meet Int Soc Study Xenobiot (ISSX). 2011, Abst. P211
81.
Uckun FM, Zheng Y, Cetkovic-Cvrlje M, Vassilev A, Lisowski E, Waurzyniak B, Chen H, Carpenter R, Chen CL: 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. Clin Cancer Res. 2002, 8 (5): 1224-1233.PubMed
82.
Uckun FM, Dibirdik I, Qazi S, Vassilev A, Ma H, Mao C, Benyumov A, Emami KH: Anti-breast cancer activity of LFM-A13, a potent inhibitor of Polo-like kinase (PLK). Bioorg Med Chem. 2007, 15 (2): 800-814. 10.1016/j.bmc.2006.10.050.CrossRefPubMed
83.
Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, Uckun FM: 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]. J Biol Chem. 1999, 274 (14): 9587-9599. 10.1074/jbc.274.14.9587.CrossRefPubMed
84.
Bam R, Ling W, Khan S, Pennisi A, Venkateshaiah SU, Li X, van Rhee F, Usmani S, Barlogie B, Shaughnessy J: Role of Bruton’s tyrosine kinase in myeloma cell migration and induction of bone disease. Am J Hematol. 2013, 88 (6): 463-471. 10.1002/ajh.23433.PubMedCentralCrossRefPubMed
85.
Brower V: BRAF inhibitors: research accelerates in wake of positive findings. J Natl Cancer Inst. 2010, 102 (4): 214-215. 10.1093/jnci/djq037.CrossRefPubMed
Metadata
Title
Ibrutinib and novel BTK inhibitors in clinical development
Authors
Akintunde Akinleye
Yamei Chen
Nikhil Mukhi
Yongping Song
Delong Liu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2013
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-6-59

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