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Protein Kinase Inhibitors

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Non-invasive decision support for NSCLC treatment using PET/CT radiomics.

Nature communications
Two major treatment strategies employed in non-small cell lung cancer, NSCLC, are tyrosine kinase inhibitors, TKIs, and immune checkpoint inhibitors, ICIs. The choice of strategy is based on heterogeneous biomarkers that can dynamically change during...

Bayesian machine learning to discover Bruton's tyrosine kinase inhibitors.

Chemical biology & drug design
Bruton's tyrosine kinase (BTK) has a crucial role in multiple cell signaling pathways including B-cell antigen receptor (BCR) and Fc receptor (FcR) signaling cascades, which has attracted much attention to find BTK inhibitors to treat autoimmune dise...

The deep learning model combining CT image and clinicopathological information for predicting ALK fusion status and response to ALK-TKI therapy in non-small cell lung cancer patients.

European journal of nuclear medicine and molecular imaging
PURPOSE: This study aimed to investigate the deep learning model (DLM) combining computed tomography (CT) images and clinicopathological information for predicting anaplastic lymphoma kinase (ALK) fusion status in non-small cell lung cancer (NSCLC) p...

Machine Learning on DNA-Encoded Libraries: A New Paradigm for Hit Finding.

Journal of medicinal chemistry
DNA-encoded small molecule libraries (DELs) have enabled discovery of novel inhibitors for many distinct protein targets of therapeutic value. We demonstrate a new approach applying machine learning to DEL selection data by identifying active molecul...

Using machine learning to improve ensemble docking for drug discovery.

Proteins
Ensemble docking has provided an inexpensive method to account for receptor flexibility in molecular docking for virtual screening. Unfortunately, as there is no rigorous theory to connect the docking scores from multiple structures to measured activ...

Machine Learning Models Based on Molecular Fingerprints and an Extreme Gradient Boosting Method Lead to the Discovery of JAK2 Inhibitors.

Journal of chemical information and modeling
Developing Janus kinase 2 (JAK2) inhibitors has become a significant focus for small-molecule drug discovery programs in recent years because the inhibition of JAK2 may be an effective approach for the treatment of myeloproliferative neoplasm. Here, ...

Novel Screening Method Identifies PI3Kα, mTOR, and IGF1R as Key Kinases Regulating Cardiomyocyte Survival.

Journal of the American Heart Association
Background Small molecule kinase inhibitors (KIs) are a class of agents currently used for treatment of various cancers. Unfortunately, treatment of cancer patients with some of the KIs is associated with cardiotoxicity, and there is an unmet need fo...

Machine Learning Models for Accurate Prediction of Kinase Inhibitors with Different Binding Modes.

Journal of medicinal chemistry
Noncovalent inhibitors of protein kinases have different modes of action. They bind to the active or inactive form of kinases, compete with ATP, stabilize inactive kinase conformations, or act through allosteric sites. Accordingly, kinase inhibitors ...

Reaction-Based Enumeration, Active Learning, and Free Energy Calculations To Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin-Dependent Kinase 2 Inhibitors.

Journal of chemical information and modeling
The hit-to-lead and lead optimization processes usually involve the design, synthesis, and profiling of thousands of analogs prior to clinical candidate nomination. A hit finding campaign may begin with a virtual screen that explores millions of comp...