PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules.
Curr Pharm Des
; 23(39): 6033-6041, 2018 02 12.
Article
en En
| MEDLINE
| ID: mdl-28982322
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Bibliotecas de Moléculas Pequeñas
/
Antígeno B7-H1
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Receptor de Muerte Celular Programada 1
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Anticuerpos
/
Neoplasias
Límite:
Animals
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Humans
Idioma:
En
Revista:
Curr Pharm Des
Asunto de la revista:
FARMACIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China