PACE4酶已被验证为扩大前列腺癌（PCa）治疗范围的有前途的治疗靶点。近年来，我们开发出一种有效的顺肽模拟抑制剂，即化合物C23（Ac-(DLeu)LLLRVK-4-amidinobenzylamide）。像许多肽一样，C23的药物特性不理想，尽管我们努力，但尚未从通常的结构活性关系研究中受益。因此，我们将注意力转向了一种新颖的制剂策略，即环糊精（CDs）的使用。CDs可以通过形成“主-客”复合物来对化合物产生益处，保护客体免受降解并增强生物存活能力。在本研究中，我们生成了一系列β-环糊精-C23复合物，并评估了它们的性质，包括对体外酶的效力、基于细胞的增殖实验和在血浆中的稳定性。结果发现了一种新的β-环糊精配方的优先化合物，除了更溶解和更强效外，还显示出改善的稳定性特性。

The enzyme PACE4 has been validated as a promising therapeutic target to expand the range of prostate cancer (PCa) treatments. In recent years, we have developed a potent peptidomimetic inhibitor, namely, compound C23 (Ac-(DLeu)LLLRVK-4-amidinobenzylamide). Like many peptides, C23 suffers from an unfavorable drug-like profile which, despite our efforts, has not yet benefited from the usual SAR studies. Hence, we turned our attention toward a novel formulation strategy, i.e., the use of cyclodextrins (CDs). CDs can benefit compounds through the formation of "host-guest" complexes, shielding the guest from degradation and enhancing biological survival. In this study, a series of βCD-C23 complexes have been generated and their properties evaluated, including potency toward the enzyme in vitro, a cell-based proliferation assay, and stability in plasma. As a result, a new βCD-formulated lead compound has been identified, which, in addition to being more soluble and more potent, also showed an improved stability profile.