Repurposing Bilastine antihistamine drug as an anti-cancer metallic drug entity: Synthesis and Single crystal X-ray structure of Metal -based Bilastine and phen {Co(II), Cu(II) & Zn(II)} tailored anticancer chemotherapeutic agents against resistant cancer cells.

Dalton Transactions, Journal Year: 2024, Volume and Issue: 53(24), P. 10126 - 10141

Published: Jan. 1, 2024

New Bilastine derived metal based drugs have been synthesized and evaluated for their anticancer potential.

Language: Английский

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Fourth-generation EGFR-TKI to overcome C797S mutation: past, present, and future

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: April 2, 2025

Overactivation of the epidermal growth factor receptor (EGFR) is prevalent in various tumours, rendering it a promising target for cancer therapy, particularly treatment non-small cell lung (NSCLC). Although first through third generations EGFR tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy, emergence drug resistance continues to pose challenge. Current research now focused on fourth-generation EGFR-TKIs, which specifically harbouring C797S mutation. This review examines design strategies, antitumor activity both vivo and vitro, binding modes, pharmacokinetics, as well advantages disadvantages each inhibitor, alongside progress clinical stage related inhibitors. Additionally, discusses future development directions aiming provide insights successful this field.

Language: Английский

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Design, Synthesis, and Antitumor Activity Evaluation of Novel 2,4,7-Trisubstituted Quinazoline Derivatives Containing an Aminomethyl Piperidine Moiety

Russian Journal of Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 51(2), P. 869 - 885

Published: April 1, 2025

Language: Английский

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Optimizing chemotherapeutic targets in non-small cell lung cancer with transfer learning for precision medicine

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0319499 - e0319499

Published: April 29, 2025

Non-small cell lung cancer (NSCLC) accounts for the majority of cases, making it most fatal diseases worldwide. Predicting NSCLC patients’ survival outcomes accurately remains a significant challenge despite advancements in treatment. The difficulties developing effective drug therapies, which are frequently hampered by severe side effects, resistance, and limited effectiveness across diverse patient populations, highlight complexity NSCLC. machine learning (ML) deep (DL) modelsare starting to reform field disclosure. These methodologies empower distinguishing proof medication targets improvement customized treatment techniques that might actually upgrade endurance results patients. Using cutting-edge methods feature extraction transfer learning, we present discovery model identification therapeutic this paper. For purpose extracting features from protein sequences, make use hybrid UNet transformer. This makes possible extract address issue false alarms. dimensionality reduction, modified Rime optimization (MRO) algorithm is used select best among multiples. In addition, design (DTransL) boost accuracy targets. Davis, KIBA, Binding-DB examples benchmark datasets validate proposed model. Results exhibit MRO+DTransL outflanks existing cutting edge models. On Davis dataset, performed better than LSTM 9.742%, achieved an 98.398%. It reached 98.264% 97.344% on KIBA datasets, respectively, indicating improvements 8.608% 8.957% over baseline

Language: Английский

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Novel PPAR-γ agonists as potential neuroprotective agents against Alzheimer's disease: rational design, synthesis, in silico evaluation, PPAR-γ binding assay and transactivation and expression studies

RSC Advances, Journal Year: 2024, Volume and Issue: 14(45), P. 33247 - 33266

Published: Jan. 1, 2024

The potential use of novel PPAR-γ agonists in the treatment Alzheimer's disease.

Language: Английский

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Atypical N-Alkyl to N-Noralkoxy Switch in a Dual cSRC/BCR-ABL1 Kinase Inhibitor Improves Drug Efflux and hERG Affinity

ACS Medicinal Chemistry Letters, Journal Year: 2023, Volume and Issue: 14(12), P. 1869 - 1875

Published: Dec. 5, 2023

We describe an atypical amine bioisostere, the trisubstituted hydroxylamine, that upon incorporation into approved dual cSRC/BCR-ABL1 kinase inhibitor yields 9, a compound retains potent biological activity and couples it with improved drug efflux hERG affinity at expense of only 2 atomic mass unit increase in molecular weight. Contrary to common expectation for hydroxylamines medicinal chemistry, 9 is well tolerated vivo lacks mutagenicity genotoxicity so often ascribed lesser substituted hydroxylamines. A matched pair (MMP) analysis suggests beneficial properties conferred by N-alkyl N-noralkoxy switch arises from reduction basicity piperazine unit. Overall, these results lend additional support use as bioisosteres groups are not involved key polar interactions.

Language: Английский

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Computationally Driven Discovery of a BCR-ABL1 Kinase Inhibitor with Activity in Multidrug-Resistant Chronic Myeloid Leukemia

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(19), P. 17820 - 17832

Published: Sept. 23, 2024

The permeability glycoprotein, encoded by the

Language: Английский

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Design, synthesis, and evaluation of antitumor activity of quinazoline derivatives containing different terminal segments of basic amine groups

Medicinal Chemistry Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Language: Английский

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