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

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 im-mune 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 applica-tion 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 re-searchers toward further investigation, thereby resulting in the discovery of different types of mole-cules, 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.