Structure-activity studies on a library of potent calix[4]arene-based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation.
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.
Zhou
Huchen
H
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Wang
De-an
DA
Baldini
Laura
L
Ennis
Eileen
E
Jain
Rishi
R
Carie
Adam
A
Sebti
Saïd M
SM
Hamilton
Andrew D
AD
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
D000970:Antineoplastic Agents; D010636:Phenols; D010982:Platelet-Derived Growth Factor; C121325:calix(4)arene; D047250:Calixarenes; D017479:Receptors, Platelet-Derived Growth Factor