AIMC Topic: Protein Kinase Inhibitors

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In silico discovery of novel compounds for FAK activation using virtual screening, AI-based prediction, and molecular dynamics.

Computational biology and chemistry
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that plays a crucial role in cell proliferation, migration, and signal transduction. FAK is overexpressed in metastatic and advanced-stage cancers, where it is considered a key kinase in c...

Computer-aided drug discovery of a dual-target inhibitor for ovarian cancer: therapeutic intervention targeting CDK1/TTK signaling pathway and structural insights in the NCI-60.

Computers in biology and medicine
Ovarian cancer remains the third most prevalent and deadliest gynecologic malignancy worldwide, with most patients eventually developing resistance to platinum-based chemotherapy. This highlights a critical unmet need for innovative multitargeted the...

Active Learning-Guided Hit Optimization for the Leucine-Rich Repeat Kinase 2 WDR Domain Based on In Silico Ligand-Binding Affinities.

Journal of chemical information and modeling
The leucine-rich repeat kinase 2 (LRRK2) is the most mutated gene in familial Parkinson's disease, and its mutations lead to pathogenic hallmarks of the disease. The LRRK2 WDR domain is an understudied drug target for Parkinson's disease, with no kno...

Drug-Drug interactions and special considerations in breast cancer patients treated with CDK4/6 inhibitors: A comprehensive review.

Cancer treatment reviews
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have reshaped the treatment paradigm of hormone receptor positive (HR + )/HER2-negative breast cancer in both adjuvant and metastatic settings. However, their metabolism via the cytochrome P450 (CYP3A4...

Design and molecular mechanism investigation of ALK inhibitors based on virtual screening and structural descriptor modeling.

Journal of receptor and signal transduction research
To address the challenges of target specificity and drug resistance in Anaplastic lymphoma kinase (ALK) inhibition, this study conducted a virtual screening of the BindingDB database, yielding 711 potential ALK inhibitors. Four QSAR models were estab...

Identification of therapeutics against PfPK6 protein of Plasmodium falciparum: Structure and Deep Learning approach.

Experimental parasitology
The Plasmodium falciparum Protein Kinase 6 (PfPK6) is a serine/threonine protein kinase categorized under the CMGC group, displaying both cyclin-dependent kinases (CDKs) and mitogen-activated protein kinases (MAPKs) activity. Previous research has in...

AI-Driven Design and Development of Nontoxic DYRK1A Inhibitors.

Journal of medicinal chemistry
Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is implicated in several human diseases, including DYRK1A syndrome, cancer, and neurodegenerative disorders such as Alzheimer's disease, making it a relevant therapeutic target. I...

Protein Profiles Predict Treatment Responses to the PI3K Inhibitor Umbralisib in Patients with Chronic Lymphocytic Leukemia.

Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE: The management of chronic lymphocytic leukemia (CLL) has significantly improved with targeted therapies. However, many patients experience a suboptimal response. To optimally select the best therapy, predictive biomarkers are necessary. In t...

Discovery of hematopoietic progenitor kinase 1 inhibitors using machine learning-based screening and free energy perturbation.

Journal of biomolecular structure & dynamics
Hematopoietic progenitor kinase 1 (HPK1) is a key negative regulator of T-cell receptor (TCR) signaling and a promising target for cancer immunotherapy. The development of novel HPK1 inhibitors is challenging yet promising. In this study, we used a c...

Increase Docking Score Screening Power by Simple Fusion With CNNscore.

Journal of computational chemistry
Scoring functions (SFs) of molecular docking is a vital component of structure-based virtual screening (SBVS). Traditional SFs yield their inherent shortage for idealized approximations and simplifications predicting the binding affinity. Complementa...