Your browser doesn't support javascript.
loading
Identification of potent inhibitors of the sortilin-progranulin interaction.
Stachel, Shawn J; Ginnetti, Anthony T; Johnson, Scott A; Cramer, Paige; Wang, Yi; Bukhtiyarova, Marina; Krosky, Daniel; Stump, Craig; Hurzy, Danielle M; Schlegel, Kelly-Ann; Cooke, Andrew J; Allen, Samantha; O'Donnell, Gregory; Ziebell, Michael; Parthasarathy, Gopal; Getty, Krista L; Ho, Thu; Ou, Yangsi; Jovanovska, Aneta; Carroll, Steve S; Pausch, Mark; Lumb, Kevin; Mosser, Scott D; Voleti, Bhavya; Klein, Daniel J; Soisson, Stephen M; Zerbinatti, Celina; Coleman, Paul J.
Afiliación
  • Stachel SJ; Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA. Electronic address: shawn_stachel@merck.com.
  • Ginnetti AT; Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Johnson SA; Department of Chemistry and Structural Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Cramer P; Department of Neuroscience, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Wang Y; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Bukhtiyarova M; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Krosky D; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Stump C; Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Hurzy DM; Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Schlegel KA; Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Cooke AJ; Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Allen S; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • O'Donnell G; Screening and Protein Science, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Ziebell M; Screening and Protein Science, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Parthasarathy G; Department of Chemistry and Structural Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Getty KL; Screening and Protein Science, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Ho T; Screening and Protein Science, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Ou Y; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Jovanovska A; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Carroll SS; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Pausch M; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Lumb K; Screening and Protein Science, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Mosser SD; Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Voleti B; Department of Neuroscience, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Klein DJ; Department of Chemistry and Structural Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Soisson SM; Department of Chemistry and Structural Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Zerbinatti C; Department of Neuroscience, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
  • Coleman PJ; Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA.
Bioorg Med Chem Lett ; 30(17): 127403, 2020 09 01.
Article en En | MEDLINE | ID: mdl-32738972
ABSTRACT
High-throughput screening methods have been used to identify two novel series of inhibitors that disrupt progranulin binding to sortilin. Exploration of structure-activity relationships (SAR) resulted in compounds with sufficient potency and physicochemical properties to enable co-crystallization with sortilin. These co-crystal structures supported observed SAR trends and provided guidance for additional avenues for designing compounds with additional interactions within the binding site.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Adaptadoras del Transporte Vesicular / Bibliotecas de Moléculas Pequeñas / Progranulinas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Adaptadoras del Transporte Vesicular / Bibliotecas de Moléculas Pequeñas / Progranulinas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2020 Tipo del documento: Article