title: Pharmacophore-based 3D-QSAR of HIF-1 inhibitors.
abstract: (Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an important new class of small molecules that inhibit the activation of hypoxia-inducible factor (HIF)-1. In order to understand the factors affecting inhibitory potency of HIF-1 inhibitors, 3 dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed. Since no receptor structure are available, the pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models gave reasonable statistics (CoMFA: q(2) = 0.564, r(2)=0.945; CoMSIA: q(2) = 0.575, r(2)=0.929). Both CoMFA and CoMSIA results indicate that the steric interaction is a major factor, while CoMSIA suggests importance of hydrogen bonding. These findings about steric and H-bonding effects can be useful to design new inhibitors.
authors.affiliation: Korea Institute of Science and Technology, Seoul, 130-650, Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Chung
authors.forename: F A
authors.initials: FA
authors.lastname: Pasha
authors.forename: Seung Joo
authors.initials: SJ
authors.lastname: Cho
authors.forename: Misun
authors.initials: M
authors.lastname: Won
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001565:Benzoates / Q000737:chemistry; D017076:Computer-Aided Design; D015195:Drug Design; D006860:Hydrogen Bonding; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D007539:Isonicotinic Acids / Q000737:chemistry; D016018:Least-Squares Analysis; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009539:Nicotinic Acids / Q000737:chemistry; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D051793:Hypoxia-Inducible Factor 1; D007539:Isonicotinic Acids; D008024:Ligands; D009539:Nicotinic Acids