COMPOUNDS

• Main Authors: ROB FALCONER, LAURENCE PATTERSON, JENNIFER ATKINSON, JASON GILL, MIKE BIBBY, LOADMAN PAUL
• Format: Patent
• Language: English; Japanese
• Published: 10.11.2016
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

PROBLEM TO BE SOLVED: To provide compounds and pharmaceutical compositions to overcome the toxic effects of systemic administration of a certain potent anticancer agent such as a vascular disrupting agent.SOLUTION: Provided is a prodrug comprising compound X associated with peptide Y where the compound X promotes microtubule formation in a manner similar to paclitaxel, and the peptide Y comprises a matrix metaloproteinase cleavage site comprising an amino acid sequence -Arg-Ser-Cit-Gly-Hof-Tyr-Leu-, where the prodrug specifically targets tumor tissues, and is selectively activated in the tumor tissues, whereby the systemic level of the active agent is reduced and the therapeutic index increases. The compound X is preferably taxane, in particular, paclitaxel.SELECTED DRAWING: None 【課題】血管破壊剤などある種の強力な抗癌剤の全身投与による毒性作用を克服する為の化合物、及び医薬組成物の提供。【解決手段】アミノ酸配列−Ａｒｇ−Ｓｅｒ−Ｃｉｔ−Ｇｌｙ−Ｈｏｆ−Ｔｙｒ−Ｌｅｕ−を含むマトリックスメタロプロテイナーゼ切断部位を含むペプチドＹと結合した、パクリタキセルに類似した方式で安定な微小管の形成を促進する化合物を含む、腫瘍組織に特異的に標的化され、または腫瘍組織において選択的に活性化され、それによって活性薬物の全身レベルが低下し、治療係数が上昇するプロドラッグ。化合物Ｘがタキサン特にパクリタキセルであることが好ましい化合物。【選択図】なし