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Minimization of drug-drug interaction risk and candidate selection in a natural product-based class of gamma-secretase modulators.
Hubbs, Jed L; Fuller, Nathan O; Austin, Wesley F; Shen, Ruichao; Ma, Jianguo; Gong, Zhen; Li, Jian; McKee, Timothy D; Loureiro, Robyn M B; Tate, Barbara; Dumin, Jo Ann; Ives, Jeffrey; Bronk, Brian S.
Afiliação
  • Hubbs JL; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA. Electronic address: jedhubbs@gmail.com.
  • Fuller NO; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Austin WF; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Shen R; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Ma J; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Gong Z; WuXi AppTec Co., Ltd, 288 Fute Zhong Road, Shanghai 200131, China.
  • Li J; WuXi AppTec Co., Ltd, 288 Fute Zhong Road, Shanghai 200131, China.
  • McKee TD; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Loureiro RM; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Tate B; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Dumin JA; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Ives J; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
  • Bronk BS; Satori Pharmaceuticals, Inc., 281 Albany Street, Cambridge, MA 02139, USA.
Bioorg Med Chem Lett ; 25(7): 1621-6, 2015 Apr 01.
Article em En | MEDLINE | ID: mdl-25708617
ABSTRACT
Early lead compounds in this gamma secretase modulator series were found to potently inhibit CYP3A4 and other human CYP isoforms increasing their risk of causing drug-drug-interactions (DDIs). Using structure-activity relationships and CYP3A4 structural information, analogs were developed that minimized this DDI potential. Three of these new analogs were further characterized by rat PK, rat PK/PD and rat exploratory toxicity studies resulting in selection of SPI-1865 (14) as a preclinical development candidate.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esteroides / Azetidinas / Produtos Biológicos / Citocromo P-450 CYP3A Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esteroides / Azetidinas / Produtos Biológicos / Citocromo P-450 CYP3A Idioma: En Ano de publicação: 2015 Tipo de documento: Article