Selective Bisubstrate Inhibitors with Sub-nanomolar Affinity for Protein Kinase Pim-1

被引：16

作者：

Ekambaram, Ramesh ^{[1
]}

Enkvist, Erki ^{[1
]}

Vaasa, Angela ^{[1
]}

Kasari, Marje ^{[1
]}

Raidaru, Gerda ^{[1
]}

Knapp, Stefan ^{[2
]}

Uri, Asko ^{[1
]}

机构：

[1] Univ Tartu, Inst Chem, EE-50411 Tartu, Estonia

[2] Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Oxford OX3 7DQ, England

来源：

CHEMMEDCHEM | 2013年 / 8卷 / 06期

基金：

英国惠康基金; 加拿大创新基金会;

关键词：

bisubstrate inhibitors; fluorescent probes; Pim-1; protein kinases; ANALOG INHIBITORS; STRUCTURAL BASIS; NONMETAL PROBES; LUMINESCENCE; SPECIFICITY; BINDING; TARGET;

D O I：

10.1002/cmdc.201300042

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Potent and selective: The unique nature of the ATP binding pocket structure of Pim family protein kinases (PKs) was used for the development of bisubstrate inhibitors and a fluorescent probe with sub-nanomolar affinity. Conjugates of arginine-rich peptides with two ATP mimetic scaffolds were synthesized and tested as inhibitors of Pim-1. Against a panel of 124 protein kinases, a novel ARC-PIM conjugate selectively inhibited PKs of the Pim family. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

收藏

页码：909 / 913

页数：5

相关论文

共 34 条

[1] The serine/threonine kinase pim-1 [J].

Bachmann, M ;

Möröy, T .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2005, 37 (04) :726-730

[2] Pim kinases in cancer: Diagnostic, prognostic and treatment opportunities [J].

Blanco-Aparicio, Carmen ;

Carnero, Amancio .

BIOCHEMICAL PHARMACOLOGY, 2013, 85 (05) :629-643

[3] PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers [J].

Brault, Laurent ;

Gasser, Christelle ;

Bracher, Franz ;

Huber, Kilian ;

Knapp, Stefan ;

Schwaller, Juerg .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (06) :1004-1015

[4] Structural basis of inhibitor specificity of the human protooncogene proviral insertion site in Moloney murine leukemia virus (PIM-1) kinase [J].

Bullock, AN ;

Debreczeni, JÉ ;

Fedorov, OY ;

Nelson, A ;

Marsden, BD ;

Knapp, S .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (24) :7604-7614

[5] Structure and substrate specificity of the Pim-1 kinase [J].

Bullock, AN ;

Debreczeni, J ;

Amos, AL ;

Knapp, S ;

Turk, BE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (50) :41675-41682

[6] Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells [J].

Chen, Lisa S. ;

Redkar, Sanjeev ;

Bearss, David ;

Wierda, William G. ;

Gandhi, Varsha .

BLOOD, 2009, 114 (19) :4150-4157

[7]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[8] Potential Use of Selective and Nonselective Pim Kinase Inhibitors for Cancer Therapy [J].

Drygin, Denis ;

Haddach, Mustapha ;

Pierre, Fabrice ;

Ryckman, David M. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (19) :8199-8208

[9] HIV-1 Tat-peptide inhibits protein kinase C and protein kinase A through substrate competition [J].

Ekokoski, Elina ;

Aitio, Olli ;

Tornquist, Kid ;

Yli-Kauhaluoma, Jari ;

Tuominen, Raimo K. .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2010, 40 (05) :404-411

[10] Carbocyclic 3′-deoxyadenosine-based highly potent bisubstrate-analog inhibitor of basophilic protein kinases [J].

Enkvist, Erki ;

Raidaru, Gerda ;

Vaasa, Angela ;

Pehk, Tonis ;

Lavogina, Daria ;

Uri, Asko .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (19) :5336-5339

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