title: Structure-activity studies on a library of potent calix[4]arene-based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation.
abstract: Platelet-derived growth factor (PDGF) and its receptor PDGFR are required for tumor growth and angiogenesis, so disruption of the PDGF-PDGFR interaction should lead to starvation of tumors and reduction of tumor growth. Potent PDGF antagonists have been discovered through the synthesis of a series of calix[4]arene-based compounds that are designed to bind to the three-loop region of PDGF. The effect of lower-rim alkylation, linker and number of interacting head groups on the calix[4]arene scaffold on PDGF affinity and cellular activity has been investigated.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Huchen
authors.initials: H
authors.lastname: Zhou
authors.forename: De-an
authors.initials: DA
authors.lastname: Wang
authors.forename: Laura
authors.initials: L
authors.lastname: Baldini
authors.forename: Eileen
authors.initials: E
authors.lastname: Ennis
authors.forename: Rishi
authors.initials: R
authors.lastname: Jain
authors.forename: Adam
authors.initials: A
authors.lastname: Carie
authors.forename: Saïd M
authors.initials: SM
authors.lastname: Sebti
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hamilton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D047250:Calixarenes / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010636:Phenols; D010982:Platelet-Derived Growth Factor; C121325:calix(4)arene; D047250:Calixarenes; D017479:Receptors, Platelet-Derived Growth Factor