Novel Peptide CM 7 Targeted c-Met with Antitumor Activity

Chunlei Xia; Ying Wang; Chen Liu; Liwen Wang; Xinmei Gao; Dongping Li; Weiyan Qi; Roujin An; Hanmei Xu

doi:10.3390/molecules25030451

Novel Peptide CM 7 Targeted c-Met with Antitumor Activity

Molecules. 2020 Jan 21;25(3):451. doi: 10.3390/molecules25030451.

Authors

Chunlei Xia^{1

2}, Ying Wang^{1

2}, Chen Liu^{1

2}, Liwen Wang^{1

2}, Xinmei Gao^{1

2}, Dongping Li^{1

2}, Weiyan Qi^{1

2}, Roujin An^{1

2}, Hanmei Xu^{1

2

3}

Affiliations

¹ The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing 211198, China.
² Department of Marine Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
³ State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 211198, China.

Abstract

Anomalous changes of the cell mesenchymal-epithelial transition factor (c-Met) receptor tyrosine kinase signaling pathway play an important role in the occurrence and development of human cancers, including gastric cancer. In this study, we designed and synthesized a novel peptide (CM 7) targeting the tyrosine kinase receptor c-Met, that can inhibit c-Met-mediated signaling in MKN-45 and U87 cells. Its affinity to human c-Met protein or c-Met-positive cells was determined, which showed specific binding to c-Met with high affinity. Its biological activities against MKN-45 c-Met-positive cells were evaluated in vitro and in vivo. As a result, peptide CM 7 exhibited moderate regulation of c-Met-mediated cell proliferation, migration, invasion, and scattering. The inhibitory effect of peptide CM 7 on tumor growth in vivo was investigated by establishing a xenograft mouse model using MKN-45 cells, and the growth inhibition rate of tumor masses for peptide CM 7 was 62%. Based on our data, CM 7 could be a promising therapeutic peptide for c-Met-dependent cancer patients.

Keywords: antitumor drug; c-Met; peptide; receptor tyrosine kinase; targeted therapy.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Drug Design
Drug Evaluation, Preclinical
Humans
Mice, Nude
Models, Molecular
Molecular Targeted Therapy*
Neoplasm Invasiveness
Peptides / chemical synthesis
Peptides / chemistry
Peptides / pharmacology*
Proto-Oncogene Proteins c-met / antagonists & inhibitors*
Proto-Oncogene Proteins c-met / metabolism
S Phase Cell Cycle Checkpoints / drug effects
Signal Transduction / drug effects

Substances

Antineoplastic Agents
Peptides
Proto-Oncogene Proteins c-met