Sci Rep:前列腺癌中白蛋白结合的肿瘤靶向前体药物研究

2019-02-28 AlexYang MedSci原创

蛋白质转换酶PACE4已经确认为是开发前列腺癌干预的新治疗方法潜在的靶标。到目前为止,能够阻断该酶活性最有效的化合物是基于一个小分子肽Ac-LLLLRVKR-NH2(即Multi-Leu(ML)肽)来设计的。该化合物的优化能够导致化合物C23(Ac-[DLeu]LLLRVK-amidinobenzylamide)的合成,并在体内具有抑制肿瘤生长的潜力。然而,PACE4抑制子还需要进一步的开发,主要

蛋白质转换酶PACE4已经确认为是开发前列腺癌干预的新治疗方法潜在的靶标。到目前为止,能够阻断该酶活性最有效的化合物是基于一个小分子肽Ac-LLLLRVKR-NH2(即Multi-Leu(ML)肽)来设计的。该化合物的优化能够导致化合物C23(Ac-[DLeu]LLLRVK-amidinobenzylamide)的合成,并在体内具有抑制肿瘤生长的潜力。然而,PACE4抑制剂还需要进一步的开发,主要是针对这些抑制剂的快速肾脏清除和增加它们的肿瘤靶向效率方面的改善。

最近,有研究人员探索了将ML肽转化进入白蛋白结合的前体药物,该前体药物具有基于前列腺特异性抗原的肿瘤特异性释放机制。研究人员的数据确认了体内ML肽的单独治疗对肿瘤的生长影响甚微,而利用ML前体药物在LNCaP异种种植小鼠中就表现出了肿瘤生长的显著减少。另外,利用携带放射性标签的上述改良药物处理表明该药物具有优秀的体内稳定性和肿瘤靶向效率。

最后,研究人员指出,他们的结果为进一步开发治疗PCa的靶向PACE4抑制剂药物提供了坚实的基础。

原始出处:

Anna Kwiatkowska, Frédéric Couture, Samia Ait-Mohand et al. Enhanced anti-tumor activity of the Multi-Leu peptide PACE4 inhibitor transformed into an albumin-bound tumor-targeting prodrug. Sci Rep. 14 Feb 2019.

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    2019-03-02 珙桐
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