PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules

Title:PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules

Volume: 23 Issue: 39

Author(s): Qiaohong Geng, Peifu Jiao*, Peng Jin, Gaoxing Su, Jinlong Dong and Bing Yan*

Affiliation:

• Department of Chemistry, Qilu Normal University, Jinan, Shandong 250013,China

• School of Environmental Science and Engineering, Shandong University, Jinan, Shandong 250100,China

Keywords: Cancer immunotherapy, therapeutic antibody, small molecules, peptides, structure-activity relationships, tumor cells.

Abstract: Background: The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD- 1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer.

Methods: The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structureactivity relationships of peptides and small molecules as inhibitors.

Results: Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors.

Conclusion: Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors.

Cite this article as:

Geng Qiaohong, Jiao Peifu*, Jin Peng , Su Gaoxing, Dong Jinlong and Yan Bing*, PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules, Current Pharmaceutical Design 2017; 23 (39) . https://dx.doi.org/10.2174/1381612823666171004120152