Discovery of a Novel and Brain-Penetrant <i>O</i>-GlcNAcase Inhibitor via Virtual Screening, Structure-Based Analysis, and Rational Lead Optimization.

Tawada, Michiko; Fushimi, Makoto; Masuda, Kei; Sun, Huikai; Uchiyama, Noriko; Kosugi, Yohei; Lane, Weston; Tjhen, Richard; Endo, Satoshi; Koike, Tatsuki

Discovery of a Novel and Brain-Penetrant O-GlcNAcase Inhibitor via Virtual Screening, Structure-Based Analysis, and Rational Lead Optimization.

Tawada, Michiko; Fushimi, Makoto; Masuda, Kei; Sun, Huikai; Uchiyama, Noriko; Kosugi, Yohei; Lane, Weston; Tjhen, Richard; Endo, Satoshi; Koike, Tatsuki.

Afiliación

Tawada M; Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi, 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
Fushimi M; Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi, 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
Masuda K; Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi, 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
Sun H; Takeda California, Inc., 9625 Towne Centre Drive, San Diego, California 92121, United States.
Uchiyama N; Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi, 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
Kosugi Y; Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi, 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
Lane W; Takeda California, Inc., 9625 Towne Centre Drive, San Diego, California 92121, United States.
Tjhen R; Takeda California, Inc., 9625 Towne Centre Drive, San Diego, California 92121, United States.
Endo S; Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi, 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
Koike T; Research, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi, 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.

J Med Chem ; 64(2): 1103-1115, 2021 01 28.

Article en En | MEDLINE | ID: mdl-33404239

Asunto(s)

Acetilglucosamina/antagonistas & inhibidores; Inhibidores Enzimáticos/síntesis química; Inhibidores Enzimáticos/farmacología; Fármacos Neuroprotectores/síntesis química; Fármacos Neuroprotectores/farmacología; beta-N-Acetilhexosaminidasas/antagonistas & inhibidores; Animales; Encéfalo/metabolismo; Línea Celular; Simulación por Computador; Diseño de Fármacos; Evaluación Preclínica de Medicamentos; Inhibidores Enzimáticos/farmacocinética; Humanos; Ratones; Ratones Endogámicos C57BL; Modelos Moleculares; Simulación del Acoplamiento Molecular; Simulación de Dinámica Molecular; Fármacos Neuroprotectores/farmacocinética; Relación Estructura-Actividad; Tauopatías/tratamiento farmacológico

Texto completo

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Acetilglucosamina / Beta-N-Acetilhexosaminidasas / Fármacos Neuroprotectores / Inhibidores Enzimáticos Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Animals / Humans Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Japón

Texto completo

Imprimir

XML

PubMed Links

Buscar en Google