Biomedical subjects

Xinshan Kang

Publications and source records attributed to Xinshan Kang.

4 recordsLinked to original sources

PubMed2006

Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.

We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth.

Animals↗

PubMed2006

Discovery and preliminary structure-activity relationship studies of novel benzotriazine based compounds as Src inhibitors.

We report the discovery and preliminary SAR studies of a series of structurally novel benzotriazine core based small molecules as inhibitors of Src kinase. To the best of our knowledge, benzotriazine template based compounds have not been reported as kinase inhibitors. The 3-(2-(1-pyrrolidinyl)ethoxy)phenyl analogue (43) was identified as one of the most potent inhibitors of Src kinase.

Humans↗

PubMed2005

Hierarchical database screenings for HIV-1 reverse transcriptase using a pharmacophore model, rigid docking, solvation docking, and MM-PB/SA.

In this work, an efficient strategy was presented to search drug leads for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) using hierarchical database screenings, which included a pharmacophore model, multiple-conformation rigid docking, solvation docking, and molecular mechanics-Poisson-Boltzmann/surface area (MM-PB/SA) sequentially. Encouraging results were achieved in searching a refined available chemical directory (ACD) database: the enrichment factor after the first three filters was estimated to be 25-fold; the hit rate for all the four filters was predicted to be 41% in a control test using 37 known HIV-1 non-nucleoside reverse transcriptase inhibitors; 10 out of 30 promising solvation-docking hits had MM-PB/SA binding free energies better than -6.8 kcal/mol and the best one, HIT15, had -17.0 kcal/mol. In conclusion, the hierarchical multiple-filter database searching strategy is an attractive strategy in drug lead exploration.

Allosteric Site↗

PubMed2004

Calculation of ligand-nucleic acid binding free energies with the generalized-born model in DOCK.

The calculation of ligand-nucleic acid binding free energies is investigated by including solvation effects computed with the generalized-Born model. Modifications of the solvation module in DOCK, including introduction of all-atom parameters and revision of coefficients in front of different terms, are shown to improve calculations involving nucleic acids. This computing scheme is capable of calculating binding energies, with reasonable accuracy, for a wide variety of DNA-ligand complexes, RNA-ligand complexes, and even for the formation of double-stranded DNA. This implementation of GB/SA is also shown to be capable of discriminating strong ligands from poor ligands for a series of RNA aptamers without sacrificing the high efficiency of the previous implementation. These results validate this approach to screening large databases against nucleic acid targets.

DNA↗