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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Current Medicinal Insights on Synthetic Small Molecules and Natural Origin Products as PD-1/PD-L1 Inhibitors

Author(s): Shivanshu Pandey, Balak Das Kurmi and Preeti Patel*

Volume 23, Issue 18, 2023

Published on: 19 May, 2023

Page: [1765 - 1781] Pages: 17

DOI: 10.2174/1568026623666230417111616

Price: $65

Abstract

Cancer is one of the leading causes of death worldwide. Each year, millions of people are diagnosed with cancer; hence, researchers have always been curious and busy developing cancer treatments. Despite thousands of studies, cancer is still a major threat to human beings. One of the mechanisms through which cancer invades a human being is the immune escape mechanism, which has been the focus of studies in the past years. PD-1/PD-L1 pathway plays a major role in this immune escape. Therefore, research focusing on blocking this pathway has led to the discovery of molecules based on monoclonal antibodies that work quite well, but despite the successful application of monoclonal antibodies as inhibitors of the PD-1/PD-L1 pathway, there are some drawbacks, such as poor bioavailability and several immune-related adverse effects, which have led the researchers toward further investigation, thereby resulting in the discovery of different types of molecules, such as small molecule inhibitors, PROTAC-based molecules, and naturally derived peptide molecules that function as inhibitors of the PD-1/PD-L1 pathway. Here, in this review, we have summarized recent findings of these molecules and focused on their structural activity relationship. The development of these molecules has opened more prospects in cancer therapy.

Keywords: Immunotherapy, Programmed death-1, PD-1/PD-L1, Immune checkpoints, Small molecule inhibitors, Natural origin inhibitors, PROTACs, Peptides.

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