Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3<i>H</i>)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor.

Huestis, Malcolm P; Dela Cruz, Darlene; DiPasquale, Antonio G; Durk, Matthew R; Eigenbrot, Charles; Gibbons, Paul; Gobbi, Alberto; Hunsaker, Thomas L; La, Hank; Leung, Dennis H; Liu, Wendy; Malek, Shiva; Merchant, Mark; Moffat, John G; Muli, Christine S; Orr, Christine J; Parr, Brendan T; Shanahan, Frances; Sneeringer, Christopher J; Wang, Weiru; Yen, Ivana; Yin, Jianping; Siu, Michael; Rudolph, Joachim

Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor.

Huestis, Malcolm P; Dela Cruz, Darlene; DiPasquale, Antonio G; Durk, Matthew R; Eigenbrot, Charles; Gibbons, Paul; Gobbi, Alberto; Hunsaker, Thomas L; La, Hank; Leung, Dennis H; Liu, Wendy; Malek, Shiva; Merchant, Mark; Moffat, John G; Muli, Christine S; Orr, Christine J; Parr, Brendan T; Shanahan, Frances; Sneeringer, Christopher J; Wang, Weiru; Yen, Ivana; Yin, Jianping; Siu, Michael; Rudolph, Joachim.

Afiliação

Huestis MP; Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Dela Cruz D; Translational Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
DiPasquale AG; Small Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Durk MR; Drug Metabolism and Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Eigenbrot C; Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Gibbons P; Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Gobbi A; Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Hunsaker TL; Translational Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
La H; Drug Metabolism and Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Leung DH; Small Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Liu W; Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Malek S; Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Merchant M; Translational Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Moffat JG; Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Muli CS; Small Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Orr CJ; Translational Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Parr BT; Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Shanahan F; Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Sneeringer CJ; Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Wang W; Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Yen I; Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Yin J; Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Siu M; Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Rudolph J; Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.

J Med Chem ; 64(7): 3940-3955, 2021 04 08.

Article em En | MEDLINE | ID: mdl-33780623

Assuntos

Neoplasias/tratamento farmacológico; Compostos de Fenilureia/uso terapêutico; Inibidores de Proteínas Quinases/uso terapêutico; Quinazolinonas/uso terapêutico; Quinases raf/antagonistas & inibidores; Animais; Azetidinas/uso terapêutico; Linhagem Celular Tumoral; Proliferação de Células/efeitos dos fármacos; Cristalografia por Raios X; Cães; Combinação de Medicamentos; Sinergismo Farmacológico; Feminino; Humanos; Células Madin Darby de Rim Canino; Camundongos Nus; Estrutura Molecular; Mutação; Compostos de Fenilureia/química; Compostos de Fenilureia/metabolismo; Piperidinas/uso terapêutico; Ligação Proteica; Inibidores de Proteínas Quinases/química; Inibidores de Proteínas Quinases/metabolismo; Quinazolinonas/química; Quinazolinonas/metabolismo; Relação Estrutura-Atividade; Ensaios Antitumorais Modelo de Xenoenxerto; Quinases raf/genética; Quinases raf/metabolismo

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos de Fenilureia / Quinases raf / Inibidores de Proteínas Quinases / Quinazolinonas / Neoplasias Limite: Animals / Female / Humans Idioma: En Revista: J Med Chem Assunto da revista: QUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

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