The multichaperone heat shock protein (Hsp) 90 complex mediates the maturation and stability of a variety of oncogenic signaling proteins. For this reason, Hsp90 has emerged as a promising target for anticancer drug development. Herein, we describe a complete computational procedure for building several 3-D QSAR models used as a ligand-based (LB) component of a comprehensive ligand-based (LB) and structure-based (SB) virtual screening (VS) protocol to identify novel molecular scaffolds of Hsp90 inhibitors. By the application of the 3-D QSAutogrid/R method, eight SB PLS 3-D QSAR models were generated, leading to a final multiprobe (MP) 3-D QSAR pharmacophoric model capable of recognizing the most significant chemical features for Hsp90 inhibition. Both the monoprobe and multiprobe models were optimized, cross-validated, and tested against an external test set. The obtained statistical results confirmed the models as robust and predictive to be used in a subsequent VS.
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SAR QSAR Environ Res
November 2024
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, India.
CDK/Cyclins are dysregulated in several human cancers. Recent studies showed inhibition of CDK4/6 was responsible for controlling cell cycle progression and cancer cell growth. In the present study, atom-based and field-based 3D-QSAR, virtual screening, molecular docking and molecular dynamics studies were done for the development of novel pyrrolo[2,3-d]pyrimidine (P2P) derivatives as anticancer agents.
View Article and Find Full Text PDFComput Biol Med
September 2024
Razi Drug Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are attractive drug targets for cancer immunotherapy. After disappointing results of the epacadostat as a selective IDO inhibitor in phase III clinical trials, there is much interest in the development of the TDO selective inhibitors. In the current study, several data analysis methods and machine learning approaches including logistic regression, Random Forest, XGBoost and Support Vector Machines were used to model a data set of compounds retrieved from ChEMBL.
View Article and Find Full Text PDFFront Chem
May 2024
Laboratory of Engineering, Modelisation and Systems Analysis, Department of Chemical Sciences, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Antiinflamm Antiallergy Agents Med Chem
January 2024
AISSMS College of Pharmacy, Pune, India.
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the joints, leading to pain, swelling, and joint deformity. Effective management of RA involves the use of disease-modifying drugs that can slow down disease progression and alleviate symptoms. Among the potential targets for RA treatment is Bruton's tyrosine kinase (BTK), which plays a crucial role in B-cell signalling and contributes to the pathogenesis of RA.
View Article and Find Full Text PDFJ Biomol Struct Dyn
November 2024
Department of Biotechnology Engineering, Sahrdaya College of Engineering and Technology, APJ Abdul Kalam Technological University of Kerala, Thrissur, Kerala, India.
Calcineurin is a serine-threonine protein phosphatase that is activated with the binding of calmodulin in the presence of increased calcium concentration and has a major role in various signaling pathways. Its role in regulating homeostasis, developmental processes, and different disease progression has already been reported. The dysregulated Ca/calcineurin/NFAT1-4 pathway is observed in Autoimmune disorders and hence the use of Calcineurin inhibitors like Cyclosporin A (CsA) and Tacrolimus (FK506) is widely done in such cases.
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