New Targets in Rheumatoid Arthritis: SYK, JAKs, and BTK

Vinall, M.; McInnes, I.

doi:10.1177/155989771113013

Cited by 1 publication

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“…Protein tyrosine kinases (PTKs) are an important class of intracellular signaling molecules that mediate cell proliferation, differentiation, and apoptosis. Some PTKs become key targets for RA, including JAK, SYK, BTK, PI3K, and so on. − At the 75th annual scientific meetings of American College of Rheumatology (ACR), Pfizer made a special report on the new RA targets SYK, BTK and JAK …”

Section: Introductionmentioning

confidence: 99%

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Activity Prediction of Small Molecule Inhibitors for Antirheumatoid Arthritis Targets Based on Artificial Intelligence

et al. 2020

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Rheumatoid arthritis (RA) is a chronic autoimmune disease, which is compared to "immortal cancer" in industry. Currently, SYK, BTK, and JAK are the three major targets of protein tyrosine kinase for this disease. According to existing research, marketed and research drugs for RA are mostly based on single target, which limits their efficacy. Therefore, designing multitarget or dual-target inhibitors provide new insights for the treatment of RA regarding of the specific association between SYK, BTK, and JAK from two signal transduction pathways. In this study, machine learning (XGBoost, SVM) and deep learning (DNN) models were combined for the first time to build a powerful integrated model for SYK, BTK, and JAK. The predictive power of the integrated model was proved to be superior to that of a single classifier. In order to accurately assess the generalization ability of the integrated model, comprehensive similarity analysis was performed on the training and the test set, and the prediction accuracy of the integrated model was specifically analyzed under different similarity thresholds. External validation was conducted using single-target and dual-target inhibitors, respectively. Results showed that our model not only obtained a high recall rate (97%) in single-target prediction, but also achieved a favorable yield (54.4%) in dual-target prediction. Furthermore, by clustering dual-target inhibitors, the prediction performance of model in various classes were proved, evaluating the applicability domain of the model in the dual-target drug screening. In summary, the integrated model proposed is promising to screen dual-target inhibitors of SYK/JAK or BTK/JAK as RA drugs, which is beneficial for the clinical treatment of rheumatoid arthritis.

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Section: Introductionmentioning

confidence: 99%

“…9−12 At the 75th annual scientific meetings of American College of Rheumatology (ACR), Pfizer made a special report on the new RA targets SYK, BTK and JAK. 13 SYK, BTK, and JAK are nonreceptor PTKs. Among them, SYK and BTK are in the B cell receptor (BCR) signaling pathway.…”

Section: ■ Introductionmentioning

confidence: 99%