Tucker Gordon C
Institut de Recherches Servier, Cancer Research Division, 125 Chemin de Ronde, 78290 Croissy sur Seine, France.
Curr Opin Investig Drugs. 2003 Jun;4(6):722-31.
Recent gene disruption experiments have suggested that targeting the alpha v integrins (cell surface adhesion and signaling receptors) to prevent tumor progression can result in different outcomes depending on the strategy. Nevertheless, two alpha v binding antagonists have made their way to the clinic in the oncology field; both Vitaxin, a humanized antibody, and cilengitide, a cyclic peptide mimicking the RGD ligand recognition peptidic domain common to alpha v integrin ligands, are in phase II clinical trials. This year, development of another peptidic inhibitor was initiated. This review questions whether companies are reluctant to propose small synthetic heterocyclic inhibitors as successors to peptide-derived agents with better pharmacokinetics and oral bioavailability. Is this class of compounds immediably flawed like the platelet alpha IIb beta 3 oral antagonists? Tentative answers are provided in this review following description of the lead compounds and the rationale for their use as cancer treatments, imaging agents or drug targeting vectors.
最近的基因破坏实验表明，针对αv整合素（细胞表面粘附和信号受体）以预防肿瘤进展，根据策略不同可能会产生不同的结果。尽管如此，两种αv结合拮抗剂已进入肿瘤学领域的临床试验；一种人源化抗体Vitaxin和一种模拟αv整合素配体共有的RGD配体识别肽结构域的环肽西仑吉肽都在进行II期临床试验。今年，另一种肽类抑制剂的研发已经启动。本综述质疑，公司是否不愿推出具有更好药代动力学和口服生物利用度的小型合成杂环抑制剂，以作为肽衍生药物的后继者。这类化合物是否像血小板αIIbβ3口服拮抗剂一样存在直接缺陷？在介绍先导化合物及其用作癌症治疗、成像剂或药物靶向载体的原理之后，本综述给出了初步答案。
