title: Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.
abstract: Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined.
authors: Amarit Bioscience, Inc., 428 Oakmead Pkwy, Sunnyvale, CA 94085, USA.
authors: Ankush
authors: A
authors: Argade
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Somasekhar
authors: S
authors: Bhamidipati
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Hui
authors: H
authors: Li
authors: UCSF, 500 Parnassus Av., San Francisco, CA 94143, USA.
authors: David
authors: D
authors: Carroll
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Jeffrey
authors: J
authors: Clough
authors: Amgen, Thousand Oaks, CA 91320, USA.
authors: Holger
authors: H
authors: Keim
authors: Genentech, 1600 Grandview Drive, South San Francisco, CA 94080, USA.
authors: Catherine
authors: C
authors: Sylvain
authors: Rossi Consulting, PO Box 734, Reedsport, OR 97467, USA.
authors: Alexander B
authors: AB
authors: Rossi
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Christina
authors: C
authors: Coquilla
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Sarkiz D
authors: SD
authors: Issakani
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Esteban S
authors: ES
authors: Masuda
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Donald G
authors: DG
authors: Payan
authors: Rigel, Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA. Electronic address: rsingh@rigel.com.
authors: Rajinder
authors: R
authors: Singh
mesh_terms: D002478:Cells, Cultured; D015195:Drug Design; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D007073:Immunoglobulin E
keywords: Cultured human mast cells (CHMC); Diaminopyrimidine; Immunoglobulin E (IgE); Tryptase