Small molecular weight protein-protein interaction antagonists -: an insurmountable challenge?

被引:99
作者
Doemling, Alexander [1 ,2 ]
机构
[1] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA
关键词
D O I
10.1016/j.cbpa.2008.04.603
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several years ago small molecular weight protein-protein interaction (PPI) antagonists were considered as the Mount Everest in drug discovery and generally regarded as too difficult to be targeted. However, recent industrial and academic research has produced a great number of new antagonists of diverse PPIs. This review structurally analyses small molecular weight PPI antagonists and their particular targets as well as tools to discover such compounds. Besides general discussions there will be a focus on the PPI p53/mdm2.
引用
收藏
页码:281 / 291
页数:11
相关论文
共 45 条
  • [11] NMR structure of a complex between MDM2 and a small molecule inhibitor
    Fry, DC
    Emerson, SD
    Palme, S
    Vu, BT
    Liu, CM
    Podlaski, F
    [J]. JOURNAL OF BIOMOLECULAR NMR, 2004, 30 (02) : 163 - 173
  • [12] A nonpeptidic sulfonamide inhibits the p53-mdm2 interaction and activates p53-dependent transcription in mdm2-overexpressing cells
    Galatin, PS
    Abraham, DJ
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (17) : 4163 - 4165
  • [13] Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells
    Grasberger, BL
    Lu, TB
    Schubert, C
    Parks, DJ
    Carver, TE
    Koblish, HK
    Cummings, MD
    LaFrance, LV
    Milkiewicz, KL
    Calvo, RR
    Maguire, D
    Lattanze, J
    Franks, CF
    Zhao, SY
    Ramachandren, K
    Bylebyl, GR
    Zhang, M
    Manthey, CL
    Petrella, EC
    Pantoliano, MW
    Deckman, IC
    Spurlino, JC
    Maroney, AC
    Tomczuk, BE
    Molloy, CJ
    Bone, RF
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (04) : 909 - 912
  • [14] Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction
    Hardcastle, IR
    Ahmed, SU
    Atkins, H
    Calvert, AH
    Curtin, NJ
    Farnie, G
    Golding, BT
    Griffin, RJ
    Guyenne, S
    Hutton, C
    Källbad, P
    Kemp, SJ
    Kitching, MS
    Newell, DR
    Norbedo, S
    Northen, JS
    Reid, RJ
    Saravanan, K
    Willems, HMG
    Lunec, J
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (05) : 1515 - 1520
  • [15] Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors
    Issaeva, N
    Bozko, P
    Enge, M
    Protopopova, M
    Verhoef, LGGC
    Masucci, M
    Pramanik, A
    Selivanova, G
    [J]. NATURE MEDICINE, 2004, 10 (12) : 1321 - 1328
  • [16] Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo
    Koblish, HK
    Zhao, SY
    Franks, CF
    Donatelli, RR
    Tominovich, RM
    LaFrance, LV
    Leonard, KA
    Gushue, JM
    Parks, DJ
    Calvo, RR
    Milkiewicz, KL
    Marugán, JJ
    Raboisson, P
    Cummings, MD
    Grasberger, BL
    Johnson, DL
    Lu, TB
    Molloy, CJ
    Maroney, AC
    [J]. MOLECULAR CANCER THERAPEUTICS, 2006, 5 (01) : 160 - 169
  • [17] NMR indicates that the small molecule RITA does not block p53-MDM2 binding in vitro
    Krajewski, M
    Ozdowy, P
    D'Silva, L
    Rothweiler, U
    Holak, TA
    [J]. NATURE MEDICINE, 2005, 11 (11) : 1135 - 1136
  • [18] Design, synthesis, and evaluation of novel boronic-chalcone derivatives as antitumor agents
    Kumar, SK
    Hager, E
    Pettit, C
    Gurulingappa, H
    Davidson, NE
    Khan, SR
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (14) : 2813 - 2815
  • [19] Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain
    Kussie, PH
    Gorina, S
    Marechal, V
    Elenbaas, B
    Moreau, J
    Levine, AJ
    Pavletich, NP
    [J]. SCIENCE, 1996, 274 (5289) : 948 - 953
  • [20] Nutlin3 blocks vascular endothelial growth factor induction by preventing the interaction between hypoxia inducible factor 1α and Hdm2
    LaRusch, Gretchen A.
    Jackson, Mark W.
    Dunbar, James D.
    Warren, Robert S.
    Donner, David B.
    Mayo, Lindsey D.
    [J]. CANCER RESEARCH, 2007, 67 (02) : 450 - 454