A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent.
Mol Cell
; 79(1): 180-190.e4, 2020 07 02.
Article
en En
| MEDLINE
| ID: mdl-32619468
ABSTRACT
Rigosertib is a styryl benzyl sulfone that inhibits growth of tumor cells and acts as a RAS mimetic by binding to Ras binding domains of RAS effectors. A recent study attributed rigosertib's mechanism of action to microtubule binding. In that study, rigosertib was obtained from a commercial vendor. We compared the purity of clinical-grade and commercially sourced rigosertib and found that commercially sourced rigosertib contains approximately 5% ON01500, a potent inhibitor of tubulin polymerization. Clinical-grade rigosertib, which is free of this impurity, does not exhibit tubulin-binding activity. Cell lines expressing mutant ß-tubulin have also been reported to be resistant to rigosertib. However, our study showed that these cells failed to proliferate in the presence of rigosertib at concentrations that are lethal to wild-type cells. Rigosertib induced a senescence-like phenotype in the small percentage of surviving cells, which could be incorrectly scored as resistant using short-term cultures.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Sulfonas
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Tubulina (Proteína)
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Proliferación Celular
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Glicina
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Neoplasias Pulmonares
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Antineoplásicos
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article