Farnesyltransferase-Mediated Delivery of a Covalent Inhibitor Overcomes Alternative Prenylation to Mislocalize K-Ras.
ACS Chem Biol
; 12(7): 1956-1962, 2017 07 21.
Article
en En
| MEDLINE
| ID: mdl-28530791
ABSTRACT
Mutationally activated Ras is one of the most common oncogenic drivers found across all malignancies, and its selective inhibition has long been a goal in both pharma and academia. One of the oldest and most validated methods to inhibit overactive Ras signaling is by interfering with its post-translational processing and subsequent cellular localization. Previous attempts to target Ras processing led to the development of farnesyltransferase inhibitors, which can inhibit H-Ras localization but not K-Ras due to its ability to bypass farnesyltransterase inhibition through alternative prenylation by geranylgeranyltransferase. Here, we present the creation of a neo-substrate for farnesyltransferase that prevents the alternative prenlation by geranylgeranyltransferase and mislocalizes oncogenic K-Ras in cells.
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Base de datos:
MEDLINE
Asunto principal:
Sistemas de Liberación de Medicamentos
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Proteínas ras
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Transporte de Proteínas
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Inhibidores Enzimáticos
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Farnesiltransferasa
Idioma:
En
Revista:
ACS Chem Biol
Año:
2017
Tipo del documento:
Article