Inhibitor kappa B kinaseb is a LDC000067? serine threonine protein kinase, which is critically involved in the activa tion of transcription factor Nuclear Factor kappa B in response to various inflammatory stimuli. I B, an inhibitory unit, is responsible for retaining NF B in the cytoplasm, for the degradation of I B by phosphorylation, and for ubiquitination to translocate NF B into the nucleolus, leading to transcription initia tion. IKKb plays a crucial role in the way of canoni cal NF B pathway, which phosphorylates I B protein and thereby translocates NF B into the nucleus and initiates pro inflammatory gene transcription. The canonical NF B pathway is well recognized in chronic inflammatory diseases and inhibition of the IKKb enzyme by a highly potent inhibitor has remained the primary goal for anti inflammatory drug discovery.
The IKK complex comprises Inhibitors,Modulators,Libraries two catalytic subunits, IKKa and IKKb, and a regulatory subunit, IKKg. Although both the catalytic subunits can catalyze the phosphorylation of I Inhibitors,Modulators,Libraries Ba, the IKKb subunit seems to play a dominant role in the canonical pathway. Further more, IKKa has a crucial Cilengitide role in mediating p52 activa tion through the non canonical pathway. IKKa can form an alternative complex and its function is required for the development of the lymphoid organ and the maturation of B cells. Ter mination of the canonical pathway by inhibiting IKKb is a potential target in anti inflammatory drug research. Recently, the virtual Inhibitors,Modulators,Libraries screening method is playing an increasingly important role in drug discovery. The structure based method involves docking of small mole cules and ranking them based on their score.
Every scoring function has its own inherent limitations, and thus, there is a high chance for reporting false positives. In order to minimize the risks of using a structure based approach, additional filters have been used to enrich the VS scheme. The application of various com putational filters in the VS cascade certainly Inhibitors,Modulators,Libraries alleviates the difficulties encountered during the initial stages of the drug discovery process. Every model used in the VS scheme has been meticulously validated by test sets that are not included in training the models. In general, the performance of the model is highly dependent on the choice of the ligand that used to train the model.
Results and discussions 3D QSAR pharmacophore model Among the 10 pharmacophore models generated, model 1 was considered to be the best, because it has the low est RMSD value and a high correlation coeffi cient between the experimental and estimated activity data of the training set. The difference between the total and the Ruxolitinib mw null hypothesis cost is 40. 21. If the dif ference is 40 60 bits, then there is a 75 90% chance that this model can represent a true correlation of the data.