Title:Current Medicinal Insights on Synthetic Small Molecules and Natural
Origin Products as PD-1/PD-L1 Inhibitors
Volume: 23
Issue: 18
Author(s): Shivanshu Pandey, Balak Das Kurmi and Preeti Patel*
Affiliation:
- Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, Moga, 142001, Punjab, India
Keywords:
Immunotherapy, Programmed death-1, PD-1/PD-L1, Immune checkpoints, Small molecule inhibitors, Natural origin inhibitors, PROTACs, Peptides.
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.
