Recent advances in the screening methods of NPC1L1 inhibitors

Zhang, Renshuai; Liu, Wenjing; Zeng, Jun; Meng, Jingsen; Shi, Lingyu; Yang, Shanbo; Chang, Jing; Wang, Chao; Xing, Kunyue; Wen, Jialian; Liu, Ning; Liang, Bing; Xing, Dongming

doi:10.1016/j.biopha.2022.113732

Cited by 9 publications

(12 citation statements)

References 62 publications

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“…There are 6 out of 14 ligands showed good intestinal absorption. Ligands (1), (3)(4), (16)(17)(18), and control were significantly absorbed, while (1), (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were poorly absorbed in the human small intestine (HIA). The greater the HIA score, the better adsorption in the intestine, where an orally administered drug's major absorption occurs [54].…”

Section: B Admet Predictionmentioning

confidence: 99%

“…All ligands were not able to present high Caco-2 permeability. However, ligands (3)(4) and (13)(14)(15)(16)(17) and control are considered to have moderately good Caco-2 permeability. To estimate the level of drug distribution, volume distribution and BBB permeability are assessed.…”

Section: B Admet Predictionmentioning

confidence: 99%

“…Cholesterol uptake is initiated by the formation and endocytosis of NPC1L1-flotillin-cholesterol membrane microdomain promoted by cholesterol. According to the findings, depletion of NTD's cholesterol-binding ability reduces the development of NPC1L1-flotillin-cholesterol membrane microdomains, impairing NPC1L1 endocytosis and cholesterol adsorption [16].…”

Section: Introductionmentioning

confidence: 98%

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The Significance of Serine of NTD-NPC1L1 for Cholesterol Binding with Compounds in Traditional Spices

Amelia¹,

Hidayat²,

Iryani³

et al. 2023

Int. J. Adv. Sci. Eng. Inf. Technol.

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It has been proposed that Niemann-Pick C1 like-1 (NPC1L1) is an intermediate membrane protein that facilitates cholesterol absorption at enterocytes, yet it is still being unknown mechanism. The study aimed to evaluate the pharmacokinetics of anti-cholesterol in traditional spices and investigate the interactions between anti-cholesterol compounds and NPC1L1. This research analyzed binding pocket, Admet, drug-likeness, the interactions, and binding affinities by DoGSiteScorer and Depth, AdmetSAR tools, and MOE.2009 software, respectively. The interactions and binding affinities were determined by molecular docking between NPC1L1 and 18 ligands derived from spices such as Cinnamon, Bay leaf, coriander, Garlic, Red Onion, Tumeric, Indosenian Chilli Pepper. Inhibitors were docked with NPC1L1 (PDB ID: 3QNT), and a comparison was made between the results of Ezetimibe, a prescribed NPC1L1 inhibitor. The Lipinski Rule of Five aids in identifying drug-like compounds and those that are not. As an octanol-water partition coefficient log P not greater than 5, all ligand including Ezetimibe has a higher affinity for the aqueous phase. 11 out of 18 inhibitors were well absorbed and distributed by forecasting oral bioavailability. Quercetin, Curcumin, and 6-Gingerol from onion, turmeric, and ginger are the potential to inhibit cholesterol absorption in the small intestine. These three highest binding energy ligands (-14.0320 to -12.3998 kcal/mol) had high binding affinities as Ezetimibe (-15.5075 kcal/mol). High binding affinities of Ezetimibe and these ligands interact at almost in the exact locations of the N-terminal domain. Through Ser_102 of N-terminal domain NPC1L1 binding with the ligands, we suggest that traditional spices of three ligands could interfere with cholesterol absorption at the early stages.

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Section: B Admet Predictionmentioning

confidence: 99%

Section: B Admet Predictionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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The Significance of Serine of NTD-NPC1L1 for Cholesterol Binding with Compounds in Traditional Spices

Amelia¹,

Hidayat²,

Iryani³

et al. 2023

Int. J. Adv. Sci. Eng. Inf. Technol.

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“…Frontiers in Pharmacology frontiersin.org cholesterol absorbed by the intestine (Zhang et al, 2022). The only NPC1L1 inhibitor currently on the market is ezetimibe (Zhang et al, 2022).…”

Section: Npc1l1mentioning

confidence: 99%

“…Frontiers in Pharmacology frontiersin.org cholesterol absorbed by the intestine (Zhang et al, 2022). The only NPC1L1 inhibitor currently on the market is ezetimibe (Zhang et al, 2022). Ezetimibe reduces plasma cholesterol levels by inhibiting NPC1L1 activity and decreasing cholesterol absorption in the intestine.…”

Section: Npc1l1mentioning

confidence: 99%

Progress of potential drugs targeted in lipid metabolism research

Liang

Dai

2022

Front. Pharmacol.

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Lipids are a class of complex hydrophobic molecules derived from fatty acids that not only form the structural basis of biological membranes but also regulate metabolism and maintain energy balance. The role of lipids in obesity and other metabolic diseases has recently received much attention, making lipid metabolism one of the attractive research areas. Several metabolic diseases are linked to lipid metabolism, including diabetes, obesity, and atherosclerosis. Additionally, lipid metabolism contributes to the rapid growth of cancer cells as abnormal lipid synthesis or uptake enhances the growth of cancer cells. This review introduces the potential drug targets in lipid metabolism and summarizes the important potential drug targets with recent research progress on the corresponding small molecule inhibitor drugs. The significance of this review is to provide a reference for the clinical treatment of metabolic diseases related to lipid metabolism and the treatment of tumors, hoping to deepen the understanding of lipid metabolism and health.

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