Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans

Journal of Pharmacology and Experimental Therapeutics

Volumn 346, Issue 2, 2013, Pages 219-228

  Evans, Erica K ^a   Tester, Richland ^a   Aslanian, Sharon ^a   Karp, Russell ^a   Sheets, Michael ^a   Labenski, Matthew T ^a   Witowski, Steven R ^a   Lounsbury, Heather ^a   Chaturvedi, Prasoon ^a   Mazdiyasni, Hormoz ^a   Zhu, Zhendong ^a   Nacht, Mariana ^a   Freed, Martin I ^a   Petter, Russell C ^a   Dubrovskiy, Alex ^a   Singh, Juswinder ^a   Westlin, William F ^a  

^a Celgene Avilomics Research   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRHEUMATIC AGENT; BRUTON TYROSINE KINASE; CC 292; N [3 [5 FLUORO 2 [4 (2 METHOXYETHOXY)PHENYLAMINO]PYRIMIDIN 4 YLAMINO]PHENYL]ACRYLAMIDE; PLACEBO; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG EFFICACY; DRUG EXPOSURE; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; NORMAL HUMAN; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RHEUMATOID ARTHRITIS;

ACRYLAMIDES; ANIMALS; ARTHRITIS, EXPERIMENTAL; ARTHRITIS, RHEUMATOID; B-LYMPHOCYTES; DOUBLE-BLIND METHOD; HUMANS; MICE; PROTEIN-TYROSINE KINASES; PYRIMIDINES; RECEPTORS, ANTIGEN, B-CELL; SIGNAL TRANSDUCTION;

EID: 84880447005     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.113.203489     Document Type: Article

References (44)

1. Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, and Chang BY, et al. (2013) Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/ refractory B-cell malignancies. J Clin Oncol 31:88-94.
2. Afar DE, Park H, Howell BW, Rawlings DJ, Cooper J, and Witte ON (1996) Regulation of Btk by Src family tyrosine kinases. Mol Cell Biol 16:3465-3471.
3. Baba Y, Hashimoto S, Matsushita M, Watanabe D, Kishimoto T, Kurosaki T, and Tsukada S (2001) BLNK mediates Syk-dependent Btk activation. Proc Natl Acad Sci USA 98:2582-2586.
4. Baran-Marszak F, Boukhiar M, Harel S, Laguillier C, Roger C, Gressin R, Martin A, Fagard R, Varin-Blank N, and Ajchenbaum-Cymbalista F, et al. (2010) Constitutive and B-cell receptor-induced activation of STAT3 are important signaling pathways targeted by bortezomib in leukemic mantle cell lymphoma. Haematologica 95:1865-1872.
5. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, and Young C, et al. (2006) R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 319:998-1008.
6. Campana D, Farrant J, Inamdar N, Webster AD, and Janossy G (1990) Phenotypic features and proliferative activity of B cell progenitors in X-linked agammaglobulinemia. J Immunol 145:1675-1680.
7. Chang BY, Huang MM, Francesco M, Chen J, Sokolove J, Magadala P, Robinson WH, and Buggy JJ (2011) The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther 13: R115.
8. Chen L, Apgar J, Huynh L, Dicker F, Giago-McGahan T, Rassenti L, Weiss A, and Kipps TJ (2005) ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia. Blood 105:2036-2041.
9. Chen L, Monti S, Juszczynski P, Daley J, Chen W, Witzig TE, Habermann TM, Kutok JL, and Shipp MA (2008) SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 111:2230-2237.
10. Conley ME (1985) B cells in patients with X-linked agammaglobulinemia. J Immunol 134:3070-3074.
11. Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, and Yang Y, et al. (2010) Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463:88-92.
12. Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, Carano RA, Darrow J, Davies DR, and DeForge LE, et al. (2011) Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol 7:41-50.
13. Edwards JC and Cambridge G (2005) Prospects for B-cell-targeted therapy in autoimmune disease. Rheumatology (Oxford) 44:151-156.
14. Edwards JC and Cambridge G (2006) B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 6:394-403.
15. Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, Schaefer-Cutillo J, De Vos S, Sinha R, and Leonard JP, et al. (2010) Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 115:2578-2585.
16. Gauld SB, Dal Porto JM, and Cambier JC (2002) B cell antigen receptor signaling: roles in cell development and disease. Science 296:1641-1642.
17. Genovese MC, Kavanaugh A, Weinblatt ME, Peterfy C, DiCarlo J, White ML, O'Brien M, Grossbard EB, and Magilavy DB (2011) An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebocontrolled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. Arthritis Rheum 63:337-345.
18. Hantschel O, Rix U, Schmidt U, Bürckstümmer T, Kneidinger M, Schütze G, Colinge J, Bennett KL, Ellmeier W, and Valent P, et al. (2007) The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci USA 104: 13283-13288.
19. Harrison C (2012) Trial watch: BTK inhibitor shows positive results in B cell malignancies. Nat Rev Drug Discov 11:96.
20. Herman SE, Gordon AL, Wagner AJ, Heerema NA, Zhao W, Flynn JM, Jones J, Andritsos L, Puri KD, and Lannutti BJ, et al. (2010) Phosphatidylinositol 3-kinased inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood 116:2078-2088.
21. Hoellenriegel J, Meadows SA, Sivina M, Wierda WG, Kantarjian H, Keating MJ, Giese N, O'Brien S, Yu A, and Miller LL, et al. (2011) The phosphoinositide 39- kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 118:3603-3612.
22. Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, and Miller RA, et al. (2010) 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 USA 107:13075-13080.
23. Khan WN, Alt FW, Gerstein RM, Malynn BA, Larsson I, Rathbun G, Davidson L, Müller S, Kantor AB, and Herzenberg LA, et al. (1995) Defective B cell development and function in Btk-deficient mice. Immunity 3:283-299.
24. Kola I and Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711-715.
25. Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, and Deininger M, et al. (2011) CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 117:591-594.
26. Lenz G, Wright GW, Emre NC, Kohlhammer H, Dave SS, Davis RE, Carty S, Lam LT, Shaffer AL, and Xiao W, et al. (2008) Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci USA 105: 13520-13525.
27. Liu L, Di Paolo J, Barbosa J, Rong H, Reif K, and Wong H (2011a) 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 338:154-163.
28. Liu Y, Zhang L, Wu Y, Tong T, Zhao W, Li P, Huang M, Wang W, Fang J, and Wei W (2011b) Therapeutic effects of TACI-Ig on collagen-induced arthritis by regulating T and B lymphocytes function in DBA/1 mice. Eur J Pharmacol 654:304-314.
29. Mangla A, Khare A, Vineeth V, Panday NN, Mukhopadhyay A, Ravindran B, Bal V, George A, and Rath S (2004) Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses. Blood 104: 1191-1197.
30. Maas A and Hendriks RW (2001) Role of Bruton's tyrosine kinase in B cell development. Dev Immunol 8:171-181.
31. Mohamed AJ, Yu L, Bäckesjö CM, Vargas L, Faryal R, Aints A, Christensson B, Berglöf A, Vihinen M, and Nore BF, et al. (2009) Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev 228:58-73.
32. Nonoyama S, Tsukada S, Yamadori T, Miyawaki T, Jin YZ, Watanabe C, Morio T, Yata J, and Ochs HD (1998) Functional analysis of peripheral blood B cells in patients with X-linked agammaglobulinemia. J Immunol 161:3925-3929.
33. Park H, Wahl MI, Afar DE, Turck CW, Rawlings DJ, Tam C, Scharenberg AM, Kinet JP, and Witte ON (1996) Regulation of Btk function by a major autophosphorylation site within the SH3 domain. Immunity 4:515-525.
34. Pighi C, Gu TL, Dalai I, Barbi S, Parolini C, Bertolaso A, Pedron S, Parisi A, Ren J, and Cecconi D, et al. (2011) Phospho-proteomic analysis of mantle cell lymphoma cells suggests a pro-survival role of B-cell receptor signaling. Cell Oncol (Dordr) 34:141-153.
35. Pine PR, Chang B, Schoettler N, Banquerigo ML, Wang S, Lau A, Zhao F, Grossbard EB, Payan DG, and Brahn E (2007) Inflammation and bone erosion are suppressed in models of rheumatoid arthritis following treatment with a novel Syk inhibitor. Clin Immunol 124:244-257.
36. Podolanczuk A, Lazarus AH, Crow AR, Grossbard E, and Bussel JB (2009) Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood 113:3154-3160.
37. Rawlings DJ, Saffran DC, Tsukada S, Largaespada DA, Grimaldi JC, Cohen L, Mohr RN, Bazan JF, Howard M, and Copeland NG, et al. (1993) Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science 261:358-361.
38. Rawlings DJ, Scharenberg AM, Park H, Wahl MI, Lin S, Kato RM, Fluckiger AC, Witte ON, and Kinet JP (1996) Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases. Science 271:822-825.
39. Saffran DC, Parolini O, Fitch-Hilgenberg M, Rawlings D, Far D, Witte ON, and Conley ME (1994) A point mutation in the SH2 domain of Bruton's tyrosine kinase in atypical X-linked agammaglobulinemia. N Engl J Med 330:1488-1491.
40. Smith CI, Bäckesjö CM, Berglöf A, Brandén LJ, Islam T, Mattsson PT, Mohamed AJ, Müller S, Nore B, and Vihinen M (1998) X-linked agammaglobulinemia: lack of mature B lineage cells caused by mutations in the Btk kinase. Springer Semin Immunopathol 19:369-381.
41. Stevenson FK, Krysov S, Davies AJ, Steele AJ, and Packham G (2011) B-cell receptor signaling in chronic lymphocytic leukemia. Blood 118:4313-4320.
42. Suljagic M, Longo PG, Bennardo S, Perlas E, Leone G, Laurenti L, and Efremov DG (2010) The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Em- TCL1 transgenic mouse model of CLL by blocking antigen-dependent Bcell receptor signaling. Blood 116:4894-4905.
43. Teng YK, Huizinga TW, and van Laar JM (2007) Targeted therapies in rheumatoid arthritis: Focus on rituximab. Biologics 1:325-333.
44. Tsukada S, Baba Y, and Watanabe D (2001) Btk and BLNK in B cell development. Adv Immunol 77:123-162.