Certepetide (CEND-1) is a novel tumor-targeting internalized arginine-glycine bifunctional cyclic peptide (a.k.a. iRGD), which is being developed for the treatment of solid tumors[1]. Certepetide aims to overcome the existing challenges in the treatment of solid tumors by delivering combined anti-cancer drugs into tumors, selectively consuming immunosuppressive T cells, enhancing the killing ability of toxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade reaction[2,3].
In vitro, when GFP-PC-3 and LM-PmC tumor cells were treated with Certepetide (10μM) for 24 hours, the random migration ability of LM-PmC and GFP-PC-3 cells in vitro was significantly inhibited, which was helpful in preventing the initial metastasis of tumor cells[2].
In vivo, Certepetide (4μmol/kg) was administered via tail vein injection in the mouse subcutaneous tumor model of liver cancer established by subcutaneous injection of HepG2 or Huh-7 cells (liver cancer cells). Certepetide can increase the concentration of sorafenib in subcutaneous tumor tissues without increasing systemic toxic effects. And enhance the killing ability of toxic T cells[4,5].
References:
[1]Winning A, Sietsema WK, Buck KK, Linsmeier A, Wiczling P. Population Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma. Clin Pharmacol Drug Dev. 2025 Mar;14(3):240-251.
[2] Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Girard OM, Hanahan D, Mattrey RF, Ruoslahti E. Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell. 2009 Dec 8;16(6):510-20.
[3] Teesalu T, Sugahara KN, Kotamraju VR, Ruoslahti E. C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16157-62.
[4] Schmithals C, Köberle V, Korkusuz H, Pleli T, Kakoschky B, Augusto EA, Ibrahim AA, Arencibia JM, Vafaizadeh V, Groner B, Korf HW, Kronenberger B, Zeuzem S, Vogl TJ, Waidmann O, Piiper A. Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma. Cancer Res. 2015 Aug 1;75(15):3147-54.
[5] McEwen A., Henson C. Quantitative whole-body autoradiography: Past, present and future. Bioanalysis. 2015;7:557–568.
Certepetide(CEND-1)是一种新型的靶向肿瘤的内化精氨酸甘氨酸双功能环肽(a.k.a. iRGD)，正在开发用于治疗实体瘤[1]。Certepetide 旨在通过将联合给药的抗癌药物输送到肿瘤中，同时选择性地消耗免疫抑制性T细胞，增强肿瘤微环境中的毒性T细胞杀伤能力，并抑制转移级联反应，从而克服治疗实体瘤的现有挑战[2,3]。
在体外，Certepetide（10μM）处理GFP-PC-3和LM-PmC肿瘤细胞24小时，显著抑制了LM-PmC和GFP-PC-3细胞的体外随机迁移能力，有助于预防肿瘤细胞初始转移[2]。
在体内，Certepetide（4μmol/kg）尾静脉注射给药于通过皮下注射HepG2或Huh-7细胞（肝癌细胞）建立的小鼠肝癌皮下瘤模型，Certepetide能提高索拉菲尼在皮下肿瘤组织的浓度，且不会增加全身毒性作用，并增强毒性T细胞的杀伤能力[4,5]。