Recent Advances in Cyclic Peptide-Based Therapeutic Strategies for Renal Cell Carcinoma: A Focused Review.

IF 6.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2026-09-29 eCollection Date: 2026-01-01 DOI:10.2147/DDDT.S638461

Liming Sun, Xiaoting Li, Yan Liu, Guangzhen Wu

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引用次数: 0

Abstract

Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), remains difficult to control after resistance to targeted therapy or immune checkpoint blockade develops. Cyclic peptides provide conformationally constrained and chemically adaptable scaffolds for direct target modulation, tumor-selective payload delivery, radiotheranostics, supramolecular assembly, and induced-proximity pharmacology. This focused mini-review groups cyclic peptide-based strategies according to the role played by the peptide in the therapeutic system. The peptide may act as the drug itself, carry a drug or radionuclide, guide a larger carrier, assemble into a drug-delivery material, or bring two proteins together. Direct RCC evidence is anchored by carbonic anhydrase IX (CAIX)-targeted DPI-4452/ZH2 radiotheranostics, cyclic Arg-Gly-Asp (cRGD)-guided small interfering RNA (siRNA) delivery to tumor endothelium, and PB1-p62-mediated polybromo 1 (PBRM1) degradation and immune sensitization. Drug-resistant non-RCC models are retained only as transferable design evidence for efflux-evasive or self-assembling delivery. We further discuss target heterogeneity, linker and assembly stability, pharmacokinetics, renal distribution, scalable synthesis, and the experimental controls required to attribute benefit to the cyclic peptide component. Although clinical therapeutic evidence remains limited, the emerging RCC-specific studies support a mechanism-matched development strategy for this drug class.

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基于环肽的肾细胞癌治疗策略的最新进展：重点综述。

肾细胞癌（RCC），尤其是透明细胞癌（ccRCC），在对靶向治疗或免疫检查点阻断产生耐药性后仍然难以控制。环状肽为直接靶向调节、肿瘤选择性负载递送、放射治疗、超分子组装和诱导接近药理学提供构象约束和化学适应性支架。这个集中的小型综述根据肽在治疗系统中所起的作用对基于环肽的策略进行分组。肽可以充当药物本身，携带药物或放射性核素，引导较大的载体，组装成药物递送材料，或将两种蛋白质结合在一起。直接的RCC证据是通过碳酐酶IX （CAIX）靶向DPI-4452/ZH2放射治疗，环状精氨酸-甘氨酸- asp （cRGD）引导的小干扰RNA （siRNA）递送到肿瘤内皮，以及pb1 -p62介导的多溴化酶1 （PBRM1）降解和免疫致敏。耐药非rcc模型仅保留作为外排逃避或自组装递送的可转移设计证据。我们进一步讨论了靶点异质性、连接物和组装稳定性、药代动力学、肾脏分布、可扩展合成和实验控制，这些都需要将环肽成分的益处归因于实验控制。尽管临床治疗证据仍然有限，但新兴的rcc特异性研究支持这类药物的机制匹配开发策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.