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

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

Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 39 , 2017

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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.

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

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Article Details

Year: 2017
Published on: 12 February, 2018
Page: [6033 - 6041]
Pages: 9
DOI: 10.2174/1381612823666171004120152
Price: $65

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