Design, synthesis and biological activity of new CDK4-specific inhibitors, based on fascaplysin

被引：42

作者：

Aubry, C

Wilson, AJ

Jenkins, PR ^{[1
]}

Mahale, S

Chaudhuri, B

Maréchal, JD

Sutcliffe, MJ

机构：

[1] Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, England

[2] De Montfort Univ, Sch Pharm, Leicester LE1 9BH, Leics, England

[3] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2006年 / 4卷 / 05期

关键词：

D O I：

10.1039/b518019h

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We present the design, synthesis, and biological activity of three classes of tryptamine derivatives, which are non-planar analogues of the toxic anti-cancer agent fascaplysin. We show these compounds to be selective inhibitors of CDK4 over CDK2, the most active compound 9q has an IC50 for the inhibition of CDK4 of 6 mu M.

引用

收藏

页码：787 / 801

页数：15

相关论文

共 29 条

[21] Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5 [J].

Meijer, L ;

Borgne, A ;

Mulner, O ;

Chong, JPJ ;

Blow, JJ ;

Inagaki, N ;

Inagaki, M ;

Delcros, JG ;

Moulinoux, JP .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 243 (1-2) :527-536

[22] PRINCIPLES OF CDK REGULATION [J].

MORGAN, DO .

NATURE, 1995, 374 (6518) :131-134

[23]

PHELPS D, 1996, METHOD ENZYMOL, V283, P194

[24] FASCAPLYSIN, AN UNUSUAL ANTIMICROBIAL PIGMENT FROM THE MARINE SPONGE FASCAPLYSINOPSIS SP [J].

ROLL, DM ;

IRELAND, CM ;

LU, HSM ;

CLARDY, J .

JOURNAL OF ORGANIC CHEMISTRY, 1988, 53 (14) :3276-3278

[25] COMPARATIVE PROTEIN MODELING BY SATISFACTION OF SPATIAL RESTRAINTS [J].

SALI, A ;

BLUNDELL, TL .

JOURNAL OF MOLECULAR BIOLOGY, 1993, 234 (03) :779-815

[26] High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: Bound waters and natural ligand as guides for inhibitor design [J].

SchulzeGahmen, U ;

DeBondt, HL ;

Kim, SH .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (23) :4540-4546

[27] Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product [J].

Soni, R ;

Muller, L ;

Furet, P ;

Schoepfer, J ;

Stephan, C ;

Zumstein-Mecker, S ;

Fretz, H ;

Chaudhuri, B .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 275 (03) :877-884

[28] CLUSTAL-W - IMPROVING THE SENSITIVITY OF PROGRESSIVE MULTIPLE SEQUENCE ALIGNMENT THROUGH SEQUENCE WEIGHTING, POSITION-SPECIFIC GAP PENALTIES AND WEIGHT MATRIX CHOICE [J].

THOMPSON, JD ;

HIGGINS, DG ;

GIBSON, TJ .

NUCLEIC ACIDS RESEARCH, 1994, 22 (22) :4673-4680

[29] Improved protein-ligand docking using GOLD [J].

Verdonk, ML ;

Cole, JC ;

Hartshorn, MJ ;

Murray, CW ;

Taylor, RD .

PROTEINS-STRUCTURE FUNCTION AND GENETICS, 2003, 52 (04) :609-623