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Identification of GDC-1971 (RLY-1971), a SHP2 Inhibitor Designed for the Treatment of Solid Tumors.
Taylor, Alexander M; Williams, Bret R; Giordanetto, Fabrizio; Kelley, Elizabeth H; Lescarbeau, André; Shortsleeves, Kelley; Tang, Yong; Walters, W Patrick; Arrazate, Alfonso; Bowman, Christine; Brophy, Erin; Chan, Emily W; Deshmukh, Gauri; Greisman, Jack B; Hunsaker, Thomas L; Kipp, D Randal; Saenz Lopez-Larrocha, Pablo; Maddalo, Danilo; Martin, Iain J; Maragakis, Paul; Merchant, Mark; Murcko, Mark; Nisonoff, Hunter; Nguyen, Vi; Nguyen, Vy; Orozco, Olivia; Owen, Christopher; Pierce, Levi; Schmidt, Molly; Shaw, David E; Smith, Sherri; Therrien, Eric; Tran, John C; Watters, Jim; Waters, Nigel J; Wilbur, Jeremy; Willmore, Lindsay.
Afiliação
  • Taylor AM; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Williams BR; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Giordanetto F; D. E. Shaw Research, 120 W. 45th St., 39th Fl., New York, New York 10036, United States.
  • Kelley EH; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Lescarbeau A; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Shortsleeves K; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Tang Y; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Walters WP; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Arrazate A; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Bowman C; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Brophy E; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Chan EW; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Deshmukh G; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Greisman JB; D. E. Shaw Research, 120 W. 45th St., 39th Fl., New York, New York 10036, United States.
  • Hunsaker TL; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Kipp DR; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Saenz Lopez-Larrocha P; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Maddalo D; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Martin IJ; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Maragakis P; D. E. Shaw Research, 120 W. 45th St., 39th Fl., New York, New York 10036, United States.
  • Merchant M; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Murcko M; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Nisonoff H; D. E. Shaw Research, 120 W. 45th St., 39th Fl., New York, New York 10036, United States.
  • Nguyen V; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Nguyen V; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Orozco O; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Owen C; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Pierce L; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Schmidt M; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Shaw DE; D. E. Shaw Research, 120 W. 45th St., 39th Fl., New York, New York 10036, United States.
  • Smith S; Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th St., New York, New York 10032, United States.
  • Therrien E; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Tran JC; Schrödinger, Inc., 1540 Broadway, 24th Floor, New York, New York 10036, United States.
  • Watters J; Genentech, Inc., 1 DNA Way Mailstop 258A, South San Francisco, California 94080-4990, United States.
  • Waters NJ; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Wilbur J; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
  • Willmore L; Relay Therapeutics, Inc., 399 Binney St., Cambridge,, Massachusetts 02139, United States.
J Med Chem ; 66(19): 13384-13399, 2023 Oct 12.
Article em En | MEDLINE | ID: mdl-37774359
ABSTRACT
Protein tyrosine phosphatase SHP2 mediates RAS-driven MAPK signaling and has emerged in recent years as a target of interest in oncology, both for treating with a single agent and in combination with a KRAS inhibitor. We were drawn to the pharmacological potential of SHP2 inhibition, especially following the initial observation that drug-like compounds could bind an allosteric site and enforce a closed, inactive state of the enzyme. Here, we describe the identification and characterization of GDC-1971 (formerly RLY-1971), a SHP2 inhibitor currently in clinical trials in combination with KRAS G12C inhibitor divarasib (GDC-6036) for the treatment of solid tumors driven by a KRAS G12C mutation.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article