Dwivedi Prarambh S R, Khanal Pukar, Gaonkar Vishakha Parab, Rasal V P, Patil B M
Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, 590010 India.
Department of Pharmacognosy and Phytochemistry, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, 590010 India.
In Silico Pharmacol. 2021 Apr 11;9(1):30. doi: 10.1007/s40203-021-00088-9. eCollection 2021.
PTP1B is identified as the insulin signaling pathway downregulator; involved in pancreatic β-cell apoptosis. Further, it associates in regulating multiple pathways in diabetes mellitus; kindled us to identify the binding affinity of bioactives from by targeting PTP1B and identify the probably associated with it; further identifying the probable pathways involved in diabetes mellitus. In this regard, ChEBI database was used to retrieve bio-actives from and 3D structures for the same were obtained from the PubChem database. The energy of bioactives was minimized and converted into ligand and the docking was carried using autodock 4.0 against PTP1B. Further, multiple characters of bio-actives like drug-likeness score, ADMET profile, probable adverse effects, and boiled egg model for bioavailability were also studied. Swertiajaponin was predicted for the highest drug-likeness score i.e. 0.26. However, swertiajaponin was predicted with the highest probable side effect of nephrotoxicity with pharmacological activity of 0.478. Similarly, swertiajaponin was predicted for the highest binding affinity with PTP1B with the binding energy of - 8.3 kcal/mol. Likewise, KEGG identified 80 pathways associated with PTP1B modulation in which 7 pathways were involved in diabetes mellitus in which FoxO signaling pathway was predicted to have the least false discovery rate by modulating 7 genes. Swertiajaponin could act as the potent inhibitor of PTP1B; scored highest druglikeness score but possessed minimum GIT absorptivity; further, PTP1B was identified to be linked with multiple pathways that are concerned with diabetes mellitus.
蛋白酪氨酸磷酸酶1B（PTP1B）被确定为胰岛素信号通路的下调因子，参与胰腺β细胞凋亡。此外，它还参与调节糖尿病的多种途径，这促使我们通过靶向PTP1B来确定生物活性物质的结合亲和力，并确定与之可能相关的物质；进一步确定糖尿病可能涉及的途径。在这方面，使用ChEBI数据库从[未提及具体来源]中检索生物活性物质，并从PubChem数据库中获得其三维结构。对生物活性物质的能量进行最小化处理并转化为配体，然后使用Autodock 4.0对PTP1B进行对接。此外，还研究了生物活性物质的多个特性，如类药性评分、ADMET概况、可能的不良反应以及生物利用度的水煮蛋模型。獐牙菜苷的类药性评分最高，即0.26。然而，獐牙菜苷被预测具有最高的肾毒性副作用可能性，药理活性为0.478。同样，獐牙菜苷被预测与PTP1B具有最高的结合亲和力，结合能为-8.3千卡/摩尔。同样，京都基因与基因组百科全书（KEGG）确定了80条与PTP1B调节相关的途径，其中7条途径与糖尿病有关，其中FoxO信号通路通过调节7个基因被预测具有最低的错误发现率。獐牙菜苷可能是PTP1B的有效抑制剂；类药性评分最高，但胃肠道吸收率最低；此外，PTP1B被确定与多个与糖尿病相关的途径有关。
