Quantitative Analysis and Pharmacokinetics Study of Integrin Antagonist AP25 in Rat Plasma

Li, Yongbing; Xu, Haiyan; Hu, Jisheng; Zhang, Fengguo; Liu, Zhendong; Zhang, Chi; Yang, Yongjing; Pu, Chunyan; Huang, Linqiu; Wen, Xin

doi:10.2174/0929866511320050012

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“…However, as a small molecular polypeptide with a molecular weight of 2.53 kDa, the half-life time of AP25 is only about 50 minutes, which greatly limits its clinical application 5. At present, chemical modification and the fusion with a large protein are the most often used method to prolong the half-life of proteins or polypeptides.…”

Section: Introductionmentioning

confidence: 99%

Anti-Tumor Activity and Pharmacokinetics of AP25-Fc Fusion Protein

Pei

Chun-ming

et al. 2019

Int. J. Med. Sci.

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AP25 is an anti-tumor peptide with a high affinity for integrins. It exerts its anti-tumor activity by inhibiting angiogenesis and by directly inhibiting the growth of tumor cells. Its half-life time in vivo is only about 50 minutes, which limits its clinical application. In order to prolong the half-life time of AP25 while preserving its anti-tumor activity, several fusion proteins of AP25 and IgG4 Fc were designed and expressed; their anti-tumor activity and pharmacokinetics properties were evaluated. Firstly, four AP25-Fc fusion protein sequences were designed, and the corresponding proteins were expressed and purified. Based on the results of HUVEC migration inhibition assay, HUVEC and tumor cell proliferation inhibition assay and yields of expression by HEK293 cells, the fusion protein designated PSG4R was selected for further evaluation. The anti-tumor effect of PSG4R was then evaluated in vivo on HCT-116 nude mice xenograft model. And the pharmacokinetics properties of PSG4R were investigated in rats. The results showed that PSG4R could inhibit the growth of xenografts of human colon cancer cell line HCT-116 in nude mice by intravenous administration of 40 mg/kg once every two days. The half-life time of PSG4R was 56.270 ± 15.398 h. This study showed that the construction of AP25-Fc fusion protein could significantly prolong the half-life of AP25 while retaining its anti-tumor activity, which provides a new direction for new drug development of AP25.

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Section: Introductionmentioning

confidence: 99%