药物从生物活性化合物的内化缀合物的选择性释放

• Format: Patent
• Language: Chinese
• Published: 27.12.2024
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

本发明涉及生物活性化合物的缀合物，其中这样的缀合物包含含有三肽的氨基酸序列，所述三肽赋予肿瘤组织匀浆进行的选择性切割以释放游离药物和/或与来自相同物种的正常组织匀浆相比提高到肿瘤组织的生物分布，其中所述正常组织是与向有需要的人类受试者施用治疗有效量的比较缀合物相关的不良事件的位点，所述比较缀合物的氨基酸序列是已知可被组织蛋白酶B选择性切割的二肽。 The invention relates to conjugates of biologically active compounds, wherein such a conjugate is comprised of a sequence of amino acids containing a tripeptide that confers selective cleavage by tumor tissue homogenate for release of free drug and/or improves biodistribution into the tumor tissue in comparison to normal tissue homogenate from the same species, wherein the normal tissue is the site of an adverse event associated with administration to a human subject in need thereof of a therapeutically effective amount of a comparator conjugate whose amino acid sequence is a dipeptide known to be selectively cleavable by Cathepsin B.