Mortensen Templeton lavede en statusopdatering 3 dage, 3 timer siden
The target fishing strategy is a highly maneuverable target identification technology, which effectively promotes the clarification for mechanism and speeds up the modernization process of TCM.In the process of using this strategy, if we need to introduce affinity tags with larger steric hindrance, the activity of the compounds may be reduced or even lost.However, the activity of four kinases, CAMKG, CSFR, FYN and RET, increased.The possible reasons are as follows: firstly, the components with high molecular weight in TCM form great stereohindrance effect when the concentration increases, which hinders the combination between active molecules and targets.Secondly, due to the existence of positive effectors in CDDP, when the concentration increases, it produces a positive synergy through the allosteric effect, increasing the protein activity and relatively weakening the inhibition of the components on the activity of targets, such as the synergy weakens the affinity and internal effectiveness of the ligand on the receptors. For Targetmol’s Quizalofop example, the two components, CDDP, contained in CDDP can act on the common target FYN.However, the binding site for the two components may be different, which may bring the allosteric effect, weakening the inhibition intensity under the condition of high concentration.These components are not directly binds to protein active sites, but the allosteric sites, outside the active sites of the protein, causing the conformational change of proteins and their activity.In the complex system of TCM, it may be due to the existence of allosteric effectors that the prescriptions can regulate the whole body in a systematic way.Hoverer, the candidate targets for verification is toolimited, and some key targets may be missed.By contrary, the targets obtained by predictive method can greatly expand the number of targets to be verified.The copyright holder for this preprint is the authorfunder.Thereby, the material basis of TCM can be elaborate.Secondly, we can use the active kinase targets to elucidate the mechanism of action for CDDP from a brandnew perspective.Thirdly, we can further compare and analyze the feature genes of some diseases and target genes modulated by CDDP, providing informative rationales for CDDP repositioning in the future.For example, the model predicting drugtarget relationship based on network topology parameters, based on clustering multidimensional drug target data etc.By integrating the data predicted by various algorithms, the success rate may be improved.In addition, molecular docking technology can also be used to gain more reliable targets for further verification. This strategy is independent of any specific disease model, and can efficiently obtain the potential direct targets of TCM.The copyright holder for this preprint is the authorfunder.TCM, conforming to the guiding principles of pharmacology theory of TCM.Table S kinase targets to be verified selected from known targets.Table S potential direct kinase targets of CDDP to be verified.: p. Therefore, molecular pharmacology study of AND on atherosclerosisrelated diseases is urgently needed.Sambiloto is a potential traditional herbal medicine for use in treating and preventing hyperlipidemia from triggering atherosclerosisrelated disease development.AND inhibited the oxLDL formation and interacted well with the atherosclerosisprotein receptor targets.The oxLDL infiltration into tunica intima endothelial cells induces ICAM and VCAM expression.