title: Identification of nonpeptidic small-molecule inhibitors of interleukin-2.
abstract: The identification, design, and synthesis of a series of novel sulfamide- and urea-based small-molecule antagonists of the protein-protein interaction IL-2/IL-2Ralpha are described. Installation of a furan carboxylic acid fragment onto a low-micromolar sulfamide resulted in a 23-fold improvement in activity, providing a sub-micromolar, nonpeptidic IL-2 inhibitor (IC(50)=0.60 microM).
authors.affiliation: Sunesis Pharmaceuticals, Inc., 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA. nwaal@sunesis.com
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Waal
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yang
authors.forename: Johan D
authors.initials: JD
authors.lastname: Oslob
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Arkin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hyde
authors.forename: Wanli
authors.initials: W
authors.lastname: Lu
authors.forename: Robert S
authors.initials: RS
authors.lastname: McDowell
authors.forename: Chul H
authors.initials: CH
authors.lastname: Yu
authors.forename: Brian C
authors.initials: BC
authors.lastname: Raimundo
mesh_terms: D006801:Humans; D020128:Inhibitory Concentration 50; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology; D014508:Urea / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013451:Sulfonic Acids; D014508:Urea; C005741:sulfamic acid