新型抗卵巢上皮腺癌药物HM-10/10模拟高密度脂蛋白肽的药代动力学和药效学研究[j]

Brittney M Wells, E. Doe, R. Farias-Eisner, Mitchell Taylor
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引用次数: 0

摘要

简介:卵巢上皮腺癌(EOC)是影响女性生殖系统的第二大常见癌症,与女性癌症相关死亡率排名第五相关。由于许多妇女在晚期出现,估计2年、5年和10年的存活率分别为65%、44%和36%。在最近的文献中,高密度脂蛋白相关载脂蛋白的作用已被证明在治疗包括癌症在内的促炎疾病中是有效的。在此之前,我们开发了一种新的20个氨基酸的模拟肽,HM-10/10,它能够在体外和体内抑制EOC模型的肿瘤发生和生长。这些发现促使我们决定进一步研究,通过进行表征来推进HM-10/10作为我们的载脂蛋白模拟肽候选选择,作为一种新的治疗EOC的药物。本研究的目的是报道HM-10/10的药代动力学(PK)和药效学(PD)特性及其体外稳定性。方法:体外多步骤评价PK/PD。结果:本品在血浆和胃环境中具有良好的稳定性。然而,在模拟小肠的条件下,HM-10/10表现出明显的降解,可能是因为其中遇到了多种肽酶。结论:这些数据突出了HM-10/10的PK/PD,并证明了其作为治疗EOC的有效药物的潜力。HM-10/10的首选给药途径是口服,为此,HM-10/10在广泛的生理pH范围内表现出显著的稳定性;然而,在模拟小肠的条件下,其稳定性明显下降。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel Anti-Ovarian Epithelial Adenocarcinoma Agent: HM-10/10 HDL-Mimetic Peptide—Pharmacokinetic and Pharmacodynamic Characterization [ID: 1377510]
INTRODUCTION: Epithelial adenocarcinoma of the ovary (EOC) is the second most common cancer affecting the female reproductive system and is associated with the fifth highest rate of cancer-related deaths in women. With many women presenting in late stages, the estimated chance of survival for 2, 5, and 10 years were 65%, 44%, and 36%, respectively. In recent literature, the role of HDL-associated apolipoproteins has been shown to be effective in the treatment of proinflammatory diseases, including cancer. Previously we developed a novel 20-amino acid mimetic peptide, HM-10/10, which was able to inhibit tumor development and growth in EOC models in vitro and in vivo. These findings prompted our decision to further our research by performing characterization to advance HM-10/10 as our apolipoprotein mimetic peptide candidate of choice for use as a novel therapeutic agent against EOC. The aim of this study was to report the pharmacokinetic (PK) and pharmacodynamic (PD) properties of HM-10/10 relative to its stability in vitro. METHODS: To evaluate PK/PD, multiple procedures were performed in vitro. RESULTS: The results demonstrated PK/PD good stability in plasma and the gastric environment. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely because of the diverse array of peptidases encountered therein. CONCLUSION: These data highlight the PK/PD of HM-10/10 and demonstrate its potential as an effective therapeutic for treating EOC. The preferred route of delivery of HM-10/10 is oral, and toward that end, HM-10/10 demonstrated remarkable stability over a broad physiologic pH range; however, its stability was significantly degraded by conditions simulating the small intestine.
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