Certepetide: A Tumor Penetrating Homing Peptide

Dr. Santosh Kumar Prajapti (Associate Professor)

Faculty of Pharmacy, Kalinga University, Raipur, (C.G.), India.

Solid tumors often remain inadequately addressed by current therapeutic regimens owing to challenges such as ineffective tumor-specific targeting, limited penetration into the tumor, and the presence of an unreceptive tumor microenvironment (TME).

Certepetide (CEND-1) is a new investigational cyclic homing peptide specifically designed to target and enhance the uptake of cytotoxic drugs into solid tumors. The drug acts on αvβ3 integrin, which is overexpressed in cancers, such as lung, gastric, pancreatic prostate, and glioma. The certepetide with RGD group (recognition site for integrin αvβ3) binds to integrin, is cleaved via proteolysis, and exposes the CRGD/K (CendR) motif.  The C-terminus of Lysine/Arginine binds to NRP-1 (neuropilin-1receptor) and activates endocytosis to introduce proteolytically cleaved RGD groups, resulting in changes in the microenvironment of the solid tumor microenvironment. This CendR mechanism leads to the effective penetration of co-administered cytotoxic drugs or drug conjugates inside tumor cells. 

A Phase 2a (double-blind, placebo-controlled, multi-center, randomized study) study is completed, where the safety profile of certepetide was compared when administered alone as well as with co-administered anticancer drugs. Clinically, Certepetide has proven to be safe, tolerable, and active when administered with nab-paclitaxel and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma.

Certepetide has potential as a novel mechanistic pathway (CendR) to improve the effectiveness of anti-cancer drugs with reduced side effects via increased access, specificity, and sensitivity towards cancer cells.

The development of certepetide represents a promising advancement in oncology, particularly in addressing the unmet needs in the treatment of solid tumors. Recognition through fast-track, orphan drug, and rare pediatric disease designations highlights its potential for significant clinical impact.