Электронный каталог

Статья

Abdeljawaad, K.A.A.
Potential P-Glycoprotein (P-gp) Inhibitors from SuperDRUG2 Database Toward Reversing Multidrug Resistance in Cancer Treatment: Database Mining, Molecular Dynamics, and Binding Energy Estimations / K.A.A.Abdeljawaad, [a.o.]. – Text : electronic // Journal of Molecular Graphics and Modelling. – 2025. – Vol. 137. – P. 108997. – URL: https://doi.org/10.1016/j.jmgm.2025.108997. – Bibliogr.: 65.

P-glycoprotein (P-gp) transporter is included in the failure of various carcinoma chemotherapeutics because of the multidrug resistance (MDR) phenomenon, in which the chemotherapeutic drugs are eliminated from target cells. Consequently, inhibiting P-gp transporter function is a prospective strategy for cancer treatment. In the current study, the SuperDRUG2 database containing >4600 pharmaceutical compounds was virtually screened toward the P-gp transporter utilizing the docking predictions. For inhibitors with a docking score lower than −10.5 kcal/mol, molecular dynamics (MD) simulations were performed, accompanied by binding energy evaluations using the MM-GBSA approach. In accordance with the MM-GBSA//100 ns MD, angiotensin amide (SD003508), terlipressin (SD002603), argipressin (SD002535), and lanreotide (SD001365) exhibited potential binding affinities against the P-gp transporter with ΔGbinding < −120.0 kcal/mol. The outstanding consistency of the investigated inhibitors inside the P-gp binding pocket was shown by the post-dynamics analyses. Additionally, MD simulations of the inhibitor-P-gp complexes in a POPC membrane environment were conducted to mimic the physiological conditions. These results demonstrated that angiotensin amide, terlipressin, argipressin, and lanreotide are promising P-gp inhibitors and deserve additional in-vitro/in-vivo studies.



Спец.(статьи,препринты) = С 44 б - Разделение химических элементов экстракционными и ионообменными методами
Спец.(статьи,препринты) = С 17 к - Расчеты по молекулярной динамике. Численное моделирование физических задач
Спец.(статьи,препринты) = 28.0 - Биология$
ОИЯИ = ОИЯИ (JINR)2025
Бюллетени = 30/025