Quest for discovering novel CDK12 inhibitor DOI
Abhijit Debnath, Rajesh Kumar Singh, Rupa Mazumder

et al.

Journal of Receptors and Signal Transduction, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Dec. 19, 2024

CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer growth facilitating macrophage invasion. a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular prostate Ewing sarcoma. It also regarded as potential biomarker, emphasizing its broader significance oncology. Targeting offers promising strategy to develop therapy. Various monoclonal antibodies have drawn wide attention, but they are expensive compared small-molecule inhibitors, limiting their accessibility affordability patients. Consequently, this research aims identify effective inhibitors using comprehensive high-throughput virtual screening. RASPD protocol has been employed screen three different databases against the target followed by drug-likeness, molecular docking, ADME, toxicity, Consensus MD Simulation,

Language: Английский

Identification of novel cyclin-dependent kinase 4/6 inhibitors from marine natural products DOI Creative Commons
Abhijit Debnath, Rupa Mazumder,

Anil Kumar Singh

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0313830 - e0313830

Published: Jan. 15, 2025

Cyclin-dependent kinases 4 and 6 (CDK4/6) are crucial regulators of cell cycle progression represent important therapeutic targets in breast cancer. This study employs a comprehensive computational approach to identify novel CDK4/6 inhibitors from marine natural products. We utilized structure-based virtual screening the CMNPD database MNP library, followed by rigorous filtering based on drug-likeness criteria, PAINS filter, ADME properties, toxicity profiles. From an initial hit 9,497 compounds, 2,344 passed filters. Further yielded 50 which 25 exhibited non-toxic These candidates underwent consensus molecular docking using seven distinct algorithms: AutoDockTools 4.2, idock, LeDock, Qvina 2, Smina, AutoDock Vina 1.2.0, PLANTS, rDock. Based these results, six top-scoring compounds were selected for 500 nanosecond all-atom dynamics simulations evaluate their structural stability interactions with CDK4/6. Our analysis revealed that CMNPD11585 CMNPD2744 demonstrated superior CDK4/6, exhibiting lower RMSD RMSF values, more favorable binding free energies, persistent hydrogen bonding patterns. also showed Solvent Accessible Surface Area indicating better compatibility active site. Subsequent in-vitro studies MTT assays MCF-7 cancer cells confirmed cytotoxic effects showing highest potency, CMNPD2744.

Language: Английский

Citations

0
Design, synthesis, docking, DFT, and MD simulation studies of new piperazine, 1,3,4-oxadiazole, and quinoline conjugates: A search for potent antiepileptic agents DOI

Shrishti Tripathi,

Rajnish Kumar, Abhijit Debnath

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108595 - 108595

Published: May 1, 2025

Language: Английский

Citations

0
Molecular landscape of lung cancer: insights into therapeutic targets and clinical outcomes DOI Creative Commons
Saloni Mangal, Abhijit Debnath, Rupa Mazumder

et al.

All Life, Journal Year: 2024, Volume and Issue: 17(1)

Published: Oct. 29, 2024

Language: Английский

Citations

1
Quest for discovering novel CDK12 inhibitor DOI
Abhijit Debnath, Rajesh Kumar Singh, Rupa Mazumder

et al.

Journal of Receptors and Signal Transduction, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Dec. 19, 2024

CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer growth facilitating macrophage invasion. a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular prostate Ewing sarcoma. It also regarded as potential biomarker, emphasizing its broader significance oncology. Targeting offers promising strategy to develop therapy. Various monoclonal antibodies have drawn wide attention, but they are expensive compared small-molecule inhibitors, limiting their accessibility affordability patients. Consequently, this research aims identify effective inhibitors using comprehensive high-throughput virtual screening. RASPD protocol has been employed screen three different databases against the target followed by drug-likeness, molecular docking, ADME, toxicity, Consensus MD Simulation,

Language: Английский

Citations

0