A-420983: a potent, orally active inhibitor of lck with efficacy in a model of transplant rejection

被引:34
作者
Borhani, DW [1 ]
Calderwood, DJ [1 ]
Friedman, MM [1 ]
Hirst, GC [1 ]
Li, BQ [1 ]
Leung, AKW [1 ]
McRae, B [1 ]
Ratnofsky, S [1 ]
Ritter, K [1 ]
Waegell, W [1 ]
机构
[1] Abbott Biores Ctr, Worcester, MA 01605 USA
关键词
D O I
10.1016/j.bmcl.2004.02.101
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
We have identified the pyrazolo[3,4-d]pyrimidine A-420983 (compound 7) as a potent inhibitor of lck. A-420983 exhibits oral efficacy in animal models of delayed-type hypersensitivity and organ transplant rejection. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2613 / 2616
页数:4
相关论文
共 12 条
  • [1] Pyrazolo[3,4-d]pyrimidines containing an extended 3-substituent as potent inhibitors of Lck -: a selectivity insight
    Burchat, AF
    Calderwood, DJ
    Friedman, MM
    Hirst, GC
    Li, BQ
    Rafferty, P
    Ritter, K
    Skinner, BS
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (12) : 1687 - 1690
  • [2] BURCHAT AF, 2002, 224 ACS NAT M BOST M
  • [3] Improved methods for transplanting split-heart neonatal cardiac grafts into the ear pinna of mice and rats
    Fey, TA
    Krause, RA
    Hsieh, GC
    Andrews, JM
    Bretheim, PT
    Morgan, SJ
    Luly, JR
    Mollison, KW
    [J]. JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 1998, 39 (01) : 9 - 17
  • [4] Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor - Study of Lck- and FynT-dependent T cell activation
    Hanke, JH
    Gardner, JP
    Dow, RL
    Changelian, PS
    Brissette, WH
    Weringer, EJ
    Pollok, K
    Connelly, PA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (02) : 695 - 701
  • [5] JUDD KP, 1971, TRANSPLANTATION, V11, P298
  • [6] Tyrosine kinase assays adapted to homogeneous time-resolved fluorescence
    Kolb, AJ
    Kaplita, PV
    Hayes, DJ
    Park, YW
    Pernell, C
    Major, JS
    Mathis, G
    [J]. DRUG DISCOVERY TODAY, 1998, 3 (07) : 333 - 342
  • [7] IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses
    Magram, J
    Connaughton, SE
    Warrier, RR
    Carvajal, DM
    Wu, CY
    Ferrante, J
    Stewart, C
    Sarmiento, U
    Faherty, DA
    Gately, MK
    [J]. IMMUNITY, 1996, 4 (05) : 471 - 481
  • [8] GENETIC-EVIDENCE FOR THE INVOLVEMENT OF THE ICK TYROSINE KINASE IN SIGNAL TRANSDUCTION THROUGH THE T-CELL ANTIGEN RECEPTOR
    STRAUS, DB
    WEISS, A
    [J]. CELL, 1992, 70 (04) : 585 - 593
  • [9] Lck regulates the tyrosine phosphorylation of the T cell receptor subunits and ZAP-70 in murine thymocytes
    vanOers, NSC
    Killeen, N
    Weiss, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (03) : 1053 - 1062
  • [10] A420983, a novel, small molecule inhibitor of LCK prevents allograft rejection
    Waegell, W
    Babineau, M
    Hart, M
    Dixon, K
    McRae, B
    Wallace, C
    Leach, M
    Ratnofsky, S
    Belanger, A
    Hirst, G
    Rossini, A
    Appel, M
    Mordes, J
    Greiner, D
    Banerjee, S
    [J]. TRANSPLANTATION PROCEEDINGS, 2002, 34 (05) : 1411 - 1417