Paper - WANFANG MED ONLINE

You Position: Home > Paper

Advances in the study of the integrin αv β3 antagonists

( views:124, downloads:17 )

Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 7

DOI:: 10.3321/j.issn:0513-4870.2006.07.001

Key Word:: 整合素αvβ3;拮抗剂;精氨酸-甘氨酸-天冬氨酸;血管生成

Abstract： @@ 肿瘤生长初期没有新血管生成(无血管期),其生长到一定程度时依赖新生血管的维持.肿瘤血管生成是肿瘤生长和转移的形态学基础,它不仅向肿瘤提供营养,也向宿主输出大量的肿瘤细胞导致肿瘤的生长和转移.因此对以抑制肿瘤血管生成为目的的抗肿瘤药物的研究方兴未艾,有很多具有抑制肿瘤血管生成作用的化合物如大黄素[1]与青蒿琥酯[2]等被发现.整合素αvβ3介导血管内皮细胞和肿瘤细胞的黏附,参与血管生成和肿瘤转移,在肿瘤生长中起重要作用.当其功能受到抑制时,血管内皮细胞出现凋亡,肿瘤生长受到抑制,甚至肿瘤消退.整合素αvβ3受体拮抗剂作为抗新生血管肿瘤药物的同时,对骨质流失[3]、血栓[4]、风湿性关节炎[5]的治疗也起了重要作用.

Reference

[1]王心华,吴淑英,甄永苏.大黄素对血管生成的抑制作用[J].2004,(4).
[2]陈欢欢,周慧君.青蒿琥酯的抗血管生成作用[J].2004,(1).
[3]Whitman D,Leu C,Prueksaritanont T,etc.Non-Peptide alpha(v)beta(3) Antagonists. Part 4: Potent and Orally Bioavailable Chain-Shortened RGD Mimetics.[J].2002,12(17).
[4]Kimmel DB,Leu CT,Prueksaritanont T,etc.Non-peptide alpha(v)beta(3) antagonists: Identification of potent, chain-shortened RGD mimetics that incorporate a central pyrrolidinone constraint.[J].2003,13(24).
[5]Motomu, Shimaoka,Timothy A, Springer.Therapeutic antagonists and conformational regulation of integrin function.[J].2003,2(9).
[6]Olivier Dormond,Agnese Mariotti,Curzio Ruegg.Endothelial cell integrins and COX-2: mediators and therapeutic targets of tumor angiogenesis[J].2004,1654(1).
[7]Hunter F,Xie J,Danthi SN,etc.Synthesis, in vitro, and in vivo characterization of an integrin alpha(v)beta(3)-targeted molecular probe for optical imaging of tumor.[J].2005,13(11).
[8]Giovanni Casiraghi,Luciana Auzzas,Gloria Rassu,etc.Grafting Aminocyclopentane Carboxylic Acids onto the RGD Tripeptide Sequence Generates Low Nanomolar alpha_v beta_3/alpha_v beta_5 Integrin Dual Binders[J].2005,48(24).
[9]Lange UE,Subkowski T,Kling A,etc.Design and synthesis of 1,5- and 2,5-substituted tetrahydrobenzazepinones as novel potent and selective integrin alpha(V)beta(3) antagonists.[J].2003,11(7).
[10]Arnaout MA,Goodman SL,Xiong JP.Coming to grips with integrin binding to ligands [Review][J].2002,14(5).
[11]Carl Manthey,Tom Markotan,Carl Crysler,etc.Design, Synthesis, and Biological Evaluation of Novel Potent and Selective alpha_vbeta_3/alpha_vbeta_5 Integrin Dual Inhibitors with Improved Bioavailability.Selection of the Molecular Core[J].2005,48(4).
[12]Marugan JJ,Leonard K,Lattanze J,etc.Non-peptidic alpha(v)beta(3) antagonists containing indol-1-yl propionic acids.[J].2005,15(10).
[13]Su Zhuang,Liu Jun O.,Dai Xuedong.An improved synthesis of a selective #alpha#_V#beta#_3-integrin antagonist cyclo(-RGDfK-)[J].2000,41(33).
[14]Culberson JC,Duggan ME,Leu CT,etc.Binding Model for Nonpeptide Antagonists of alpha(v)beta(3) Integrin.[J].2002,45(26).
[15]Seitz W,Zechel C,Graef C,etc.Highly potent and selective alpha(V)beta(3)-receptor antagonists: solid-phase synthesis and SAR of 1-substituted 4-amino-1H-pyrimidin-2-ones.[J].2003,13(2).
[16]Bubenik M,Meerovitch K,Attardo G,etc.A novel RGD antagonist that targets both alphavbeta3 and alpha5beta1 induces apoptosis of angiogenic endothelial cells on type I collagen.[J].2003,40(2).
[17]Ghosh S,Santulli RJ,Tuman RW,etc.Piperidine-containing beta-arylpropionic acids as potent antagonists of alpha(v)beta(3)/alpha(v)beta(5) integrins.[J].2004,14(20).
[18]Zi-Fen Su,Mary Rusckowski,Donald J. Hantowich,etc.In Vitro and in Vivo Evaluation of a Technetium-99m-Labeled Cyclic RGD Peptide as a Specific Marker of #alpha#v#beta#_3 Integrin for Tumor Imaging[J].2002,13(3).
[19]Morie T,Iwama S,Notake M,etc.Discovery of a potent and selective alpha v beta 3 integrin antagonist with strong inhibitory activity against neointima formation in rat balloon injury model.[J].2004,14(10).
[20]Santulli RJ,Galemmo RA Jr,Decorte BL,etc.1,2,3,4-Tetrahydroquinoline-containing alpha(V)beta(3) integrin antagonists with enhanced oral bioavailability.[J].2004,14(23).
[21]Leonardo Manzoni,Anna Checchia,Giuseppe Giannini,etc.Potent Integrin Antagonists from a Small Library of RGD-Including Cyclic Pseudopeptides[J].2001,3(7).
[22]Han N,Tasker AS,Zhang J,etc.N-Aryl-gamma-lactams as integrin alphavbeta3 antagonists.[J].2004,14(11).
[23]Kopecek J,Kopeckova P,Wang D,etc.Bone-targeting macromolecular therapeutics.[J].2005,57(7).
[24]Tucker GC,Perron Sierra F,Saint Dizier D,etc.Substituted benzocyloheptenes as potent and selective alpha(v) integrin antagonists.[J].2002,12(22).
[25]STUPACK, D.G.,STORGARD, C.M.,CHERESH, D.A..A role for angiogenesis in rheumatoid arthritis.[J].1999,32(5).