The relationship between rational drug design and drug side effects.
Brief Bioinform
; 13(3): 377-82, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-21949217
ABSTRACT
Previous analysis of systems pharmacology has revealed a tendency of rational drug design in the pharmaceutical industry. The targets of new drugs tend to be close with the corresponding disease genes in the biological networks. However, it remains unclear whether the rational drug design introduces disadvantages, i.e. side effects. Therefore, it is important to dissect the relationship between rational drug design and drug side effects. Based on a recently released drug side effect database, SIDER, here we analyzed the relationship between drug side effects and the rational drug design. We revealed that the incidence drug side effect is significantly associated with the network distance of drug targets and diseases genes. Drugs with the distances of three or four have the smallest incidence of side effects, whereas drugs with the distances of more than four or smaller than three show significantly greater incidence of side effects. Furthermore, protein drugs and small molecule drugs show significant differences. Drugs hitting membrane targets and drugs hitting cytoplasm targets also show differences. Failure drugs because of severe side effects show smaller network distances than approved drugs. These results suggest that researchers should be prudent on rationalizing the drug design. Too small distances between drug targets and diseases genes may not always be advantageous for rational design for drug discovery.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Idioma:
En
Revista:
Brief Bioinform
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
China