Chemical Synthetic Approaches to Mimic the TRAIL: Promising Cancer Therapeutics

Overview

Journal RSC Med Chem

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Sep 9

PMID 39246747

Authors

Abdullah-Al Masum

Shin Aoki

Md Mahbubur Rahman

Yosuke Hisamatsu

Affiliations

Soon will be listed here.

Abstract

Apoptosis is programmed cell death that eliminates undesired cells to maintain homeostasis in metazoan. Aberration of this process may lead to cancer genesis. The tumor necrosis factor related apoptosis inducing ligand (TRAIL) induces apoptosis in cancer cells after ligation with death receptors (DR4/DR5) while sparing most normal cells. Therefore, strategies to induce apoptosis in cancer cells by mimicking the TRAIL emerge as a promising therapeutic tool. Hence, approaches are taken to develop TRAIL/DR-based cancer therapeutics. The recombinant soluble TRAIL (rhTRAIL) and death receptor agonistic antibodies were produced and tested pre-clinically and clinically. Pre-clinical and clinical trial data demonstrate that these therapeutics are safe and relatively well tolerated. But some of these therapeutics failed to exert adequate efficacy in clinical settings. Besides these biotechnologically derived therapeutics, a few chemically synthesized therapeutics are reported. Some of these therapeutics exert considerable efficacy and . In this review, we will discuss chemically synthesized TRAIL/DR-based therapeutics, their chemical and biological behaviour, design concepts and strategies that may contribute to further improvement of TRAIL/DR-based therapeutics.

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