Receptor guided 3D-QSAR: A useful approach for designing of IGF-1R inhibitors
- Authors
- Muddassar, M.; Pasha, F. A.; Chung, H. W.; Yoo, K. H.; Oh, C. H.; Cho, S. J.
- Issue Date
- 2008-03
- Publisher
- HINDAWI LTD
- Citation
- JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY
- Abstract
- Research by other investigators has established that insulin-like growth factor-1 receptor (IGF-1R) is a key oncological target, and that derivatives of 1, 3-disubstituted-imidazo[ 1,5-alpha] pyrazine are potent IGF-1R inhibitors. In this paper, we report on our three-dimensional quantitative structure activity relationship (3D-QSAR) studies for this series of compounds. We validated the 3D-QSAR models by the comparison of two major alignment schemes, namely, ligand-based (LB) and receptor-guided (RG) alignment schemes. The latter scheme yielded better 3D-QSAR models for both comparative molecular field analysis (CoMFA) (q(2) = 0.53, r(2) = 0.95) and comparative molecular similarity indices analysis (CoMSIA) (q(2) = 0.51, r(2) = 0.86). We submit that this might arise from the more accurate inhibitor alignment that results from using the structural information of the active site. We conclude that the receptor-guided 3D-QSAR may be helpful to design more potent IGF-1R inhibitors, as well as to understand their binding affinity with the receptor. Copyright (c) 2008 M. Muddassar et al.
- Keywords
- GROWTH-FACTOR-I; BREAST-CANCER; COMFA; MOLECULES; KINASE; COMSIA; FIELD; QSAR; GROWTH-FACTOR-I; BREAST-CANCER; COMFA; MOLECULES; KINASE; COMSIA; FIELD; QSAR; 3D QSAR; molecular docking; receptor-guided alignment; inhibitors
- ISSN
- 1110-7243
- URI
- https://pubs.kist.re.kr/handle/201004/133700
- DOI
- 10.1155/2008/837653
- Appears in Collections:
- KIST Article > 2008
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