Structure-guided optimization of a novel class of ASK1 inhibitors with increased sp<sup>3</sup> character and an exquisite selectivity profile.

Bigi-Botterill, Simone V; Ivetac, Anthony; Bradshaw, Erica L; Cole, Derek; Dougan, Douglas R; Ermolieff, Jacques; Halkowycz, Petro; Johnson, Ben; McBride, Christopher; Pickens, Jason; Sabat, Mark; Swann, Steven

Structure-guided optimization of a novel class of ASK1 inhibitors with increased sp³ character and an exquisite selectivity profile.

Bigi-Botterill, Simone V; Ivetac, Anthony; Bradshaw, Erica L; Cole, Derek; Dougan, Douglas R; Ermolieff, Jacques; Halkowycz, Petro; Johnson, Ben; McBride, Christopher; Pickens, Jason; Sabat, Mark; Swann, Steven.

Afiliación

Bigi-Botterill SV; Medicinal Chemistry & In Vitro Pharmacology, Gastroenterology Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States. Electronic address: simone.bigi@takeda.com.
Ivetac A; Mirati Therapeutics, 9393 Towne Centre Drive #200, San Diego, CA 92121, United States.
Bradshaw EL; Quantitative Translational Sciences, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
Cole D; Medicinal Chemistry & In Vitro Pharmacology, Gastroenterology Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
Dougan DR; Structural Biology & Biophysics, Gastroenterology Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
Ermolieff J; Medicinal Chemistry & In Vitro Pharmacology, Gastroenterology Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
Halkowycz P; Medicinal Chemistry & In Vitro Pharmacology, Gastroenterology Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
Johnson B; Medicinal Chemistry, Neuroscience Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
McBride C; 858 Therapeutics, 4757 Nexus Center Drive #150, San Diego, CA 92121, United States.
Pickens J; Medicinal Chemistry & In Vitro Pharmacology, Gastroenterology Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
Sabat M; Medicinal Chemistry & In Vitro Pharmacology, Gastroenterology Drug Discovery Unit, Takeda Research in California, 9625 Towne Centre Drive, San Diego, CA 92121, United States.
Swann S; Chemistry & Design, Silicon Therapeutics, 451 D Street #205, Boston, MA 02210, United States.

Bioorg Med Chem Lett ; 30(17): 127405, 2020 09 01.

Article en En | MEDLINE | ID: mdl-32738982

Asunto(s)

MAP Quinasa Quinasa Quinasa 5/antagonistas & inhibidores; Inhibidores de Proteínas Quinasas/química; Animales; Sitios de Unión; Dominio Catalítico; Cristalografía por Rayos X; Diseño de Fármacos; Humanos; Imidazoles/química; Imidazoles/metabolismo; Imidazoles/uso terapéutico; Concentración 50 Inhibidora; MAP Quinasa Quinasa Quinasa 5/metabolismo; Ratones; Simulación de Dinámica Molecular; Daño por Reperfusión Miocárdica/tratamiento farmacológico; Inhibidores de Proteínas Quinasas/metabolismo; Inhibidores de Proteínas Quinasas/uso terapéutico

Palabras clave

Apoptosis Signal-Regulating Kinase-1 (ASK1); Cardiac injury; Kinome selectivity; Mitogen-Activated Protein Kinase Kinase Kinase (MAP3K); Structure-Based Drug Design (SBDD)

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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: MAP Quinasa Quinasa Quinasa 5 / Inhibidores de Proteínas Quinasas Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2020 Tipo del documento: Article

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