αV integrin is a protein that is encoded by the ITGAV gene. Studies show the participation of αV integrins in the proliferation, motility and proteolysis of various cancer cells. Neuropilin-1 is a membrane-bound coreceptor to a tyrosine kinase receptor for both vascular endothelial growth factor and semaphorin family members. While Neuropilin 1 shows interaction with Vascular endothelial growth factor A. Specifically, Neuropilin 1 shows implications for the vascularization and progression of cancers. Besides, Neuropilin 1 expresses in several human patient tumor samples, including brain, prostate, breast, colon, and lung cancer.

Certepetide targets αV integrins and neuropilin-1 and enhances tumor delivery of co-administered anticancer drugs.

Certepetide (CEND-1) is a bifunctional cyclic peptide (a.k.a. iRGD). Importantly, Certepetide homes to tumors via RGD tumor homing motif interaction with alpha v-integrins. Meanwhile, Certepetide leads to the transformation of the solid tumor microenvironment into a temporary drug conduit via interaction with neuropilin-1. And leads to an enhanced tumor delivery of co-administered anti-cancer agents. Certepetide is a tumor-penetrating peptide with a cyclizing (S-S bond through the cysteine side chains) structure containing nine amino acids. Besides, Certepetide increases the accumulation and penetration of anticancer drugs into tumors, but not into normal tissues. As a result, enhances the anti-tumor activity and improves the therapeutic margins/safety profile. In addition, Certepetide is administered before the subsequent and sequential administration of one or more anti-cancer agents. Furthermore, Certepetide combines with gemcitabine and nab-paclitaxel shows anti-tumor activity in metastatic pancreatic ductal adenocarcinoma. All in all, Certepetide is a tumor-penetrating enhancer that targets αV integrins and neuropilin-1 and enhances tumor delivery of co-administered anticancer drugs.