The discovery of potent and stable short peptide FGFR1 antagonist for cancer therapy.,European Journal of Pharmaceutical Sciences

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The discovery of potent and stable short peptide FGFR1 antagonist for cancer therapy.
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2019-12-10 , DOI: 10.1016/j.ejps.2019.105179
Jianzhang Wu ₁ , Lingzi Chen ₁ , Liping Chen ₂ , Lei Fan ₁ , Zhe Wang ₁ , Zhaojun Dong ₁ , Qian Chen ₁ , Tao Wei ₁ , Yuepiao Cai ₁ , Wulan Li ₃

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Fibroblast growth factor receptor 1 (FGFR1) is one of the attractive pharmaceutical targets for cancer therapy. The FGFR1 targeting antagonist peptides, especially of the short peptides harbouring only coding amino acid might highlights promising aspects for their higher affinity, specificity and lower adverse reactions. However, most of peptides inhibitors remain in preclinical research, likely associating with their instability and short half-life. In this study, we found a stable short peptide inhibitor P48 and speculated that its stability might be related to its non-linear spatial structure. In addition, P48 could target the extracellular immunoglobulin domain of FGFR1, and effectively block the particular signaling pathways of FGFR1, which lead to the inhibition of cancer proliferation, invasion in vitro and restraint of tumor growth in vivo. Together, this study provided a promising FGFR1 inhibitor with the potential to be developed as an antitumor drug.

中文翻译：

有效和稳定的短肽FGFR1拮抗剂用于癌症治疗的发现。

成纤维细胞生长因子受体1（FGFR1）是用于癌症治疗的诱人药物靶标之一。靶向FGFR1的拮抗肽，尤其是仅包含编码氨基酸的短肽，可能因其较高的亲和力，特异性和较低的不良反应而突出了有希望的方面。但是，大多数肽抑制剂仍处于临床前研究中，可能与其不稳定性和半衰期短有关。在这项研究中，我们发现了稳定的短肽抑制剂P48，并推测其稳定性可能与其非线性空间结构有关。另外，P48可以靶向FGFR1的细胞外免疫球蛋白结构域，并有效地阻断FGFR1的特定信号传导途径，从而导致抑制癌症的增殖，体外侵袭和体内肿瘤生长的抑制。

更新日期：2019-12-11

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