Peptidomimetics Targeting Cancer: Trends and Recent Applications

Considerable efforts have been focused on cancer treatment for decades in a global sense.
However, cancer is still a top target that necessitates us to deliver more effective and safer drugs to the patients. Here is a recent review on peptidomimetics in cancer targeting.¹⁾ This review would allow us better understanding of the potential of peptidomimetics in the field of cancer and also other diseases.

Peptidomimetics are novel molecular entities in pharmaceutical sciences which serve as alternatives of natural or unnatural peptides. Peptides are traditional and well-known drug class and numerous trials have been made for the development of cancer drugs.
However, there are huge obstacles like stability, delivery, immunogenicity, toxicity and so on.
In order to overcome these limitations, peptidomimetics have been developed over the years. PepMetics^®is one of this molecular class and, in cancer field, E7386 is currently under phase 1b/2 trial, thanks to Eisai Co., Ltd..

The potential usages of peptidomimetics are classified, according to the review, to 5 classes: cancer diagnosis, angiogenesis inhibition, apoptosis triggering, cancer proliferation targeting, and metastasis inhibition.
Among them, cancer proliferation targeting has been the most intense class of cancer drug development in the field of peptidomimetics. ER-α (SRC2-SP3, PERM1, and ER-1b)²⁾ and FGF2 (P29)³⁾ are the good examples of peptidomimetics applications.
Angiogenesis, apoptosis and metastasis have also been the focused classes and numerous studies are summarized in this review.
Currently, cancer diagnosis gathers more interest and ⁶⁸Ga-NODAGA-THERANOST^™ (Advanced Imaging Projects, LLC) are under phase 2 (NCT04480619) for diagnosis and clinical management in angiogenic breast cancer patients.⁴⁾

Peptidomimetics open up a great opportunity to overcome cancer drug resistance as well. Lys-P⁵⁾ and TTT-28⁶⁾ are representative and potent peptidomimetics for multidrug resistance (MDR). These molecules were revealed to reverse P-glycoprotein (P-gp/ABCB1/MDR1)⁷⁾ -mediated MDR in different mechanisms.

A wide range of cancer treatment approaches has been applied in peptidomimetics and up to now promising study results have shown at least in the research stage. Several anticancer drug candidates are also under clinical trials and the top runners are under phase 3 (e.g., cilengitide, NCT00689221).

We are also trying PepMetics^® for the treatment of cancer. Owing to Eisai’s clinical trial, our scaffold is revealed promising as a tolerable and effective drug development.
If you are interested in peptidomimetics and/or cancer treatment drug discovery, please contact us for discussion. Our platform technology would help you to find hits on the interested target in cancer field.

1) https://doi.org/10.1186/s10020-022-00577-3
2) https://doi.org/10.1016/j.bmcl.2018.05.062
3) https://doi.org/10.1097/cad.0000000000000312
4) https://doi.org/10.1089/cbr.2014.1747
5) https://doi.org/10.1016/j.ijpharm.2011.12.046
6) https://doi.org/10.1038/srep42106
7) https://doi.org/10.1002/cpt.2670