Discovery and in Vivo Evaluation of Macrocyclic Mcl-1 Inhibitors Featuring an α-Hydroxy Phenylacetic Acid Pharmacophore or Bioisostere.
J Med Chem
; 62(22): 10258-10271, 2019 11 27.
Article
en En
| MEDLINE
| ID: mdl-31736296
ABSTRACT
Overexpression of the antiapoptotic protein Mcl-1 provides a survival advantage to some cancer cells, making inhibition of this protein an attractive therapeutic target for the treatment of certain types of tumors. Herein, we report our efforts toward the identification of a novel series of macrocyclic Mcl-1 inhibitors featuring an α-hydroxy phenylacetic acid pharmacophore or bioisostere. This work led to the discovery of 1, a potent Mcl-1 inhibitor (IC50 = 19 nM in an OPM-2 cell viability assay) with good pharmacokinetic properties and excellent in vivo efficacy in an OPM-2 multiple myeloma xenograft model.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fenilacetatos
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Proteína 1 de la Secuencia de Leucemia de Células Mieloides
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2019
Tipo del documento:
Article