更新于：2024-11-01

PPARα x PPARγ x DPP-4

更新于：2024-11-01

基本信息

关联

项与 PPARα x PPARγ x DPP-4 相关的药物

Lobeglitazone/Sitagliptin

洛贝格列酮/西格列汀

靶点

DPP-4 x PPARα x PPARγ

作用机制

DPP-4抑制剂 [+2]

在研机构-

原研机构

Chong Kun Dang Pharmaceutical Corp.

在研适应症-

非在研适应症

2型糖尿病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 PPARα x PPARγ x DPP-4 相关的临床试验

NCT04246190 / Unknown status临床1期

A Randomized, Open-label, Single-dose, Two-way Crossover Clinical Trial to Investigate the Pharmacokinetics and Safety After Oral Administration of CKD-396 and Co-administration of CKD-501 and D759 in Healthy Adults

The purpose of this study is to evaluate the pharmacokinetics and safety of CKD-396.

开始日期2020-02-24

申办/合作机构

Chong Kun Dang Pharmaceutical Corp.

100 项与 PPARα x PPARγ x DPP-4 相关的临床结果

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100 项与 PPARα x PPARγ x DPP-4 相关的转化医学

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0 项与 PPARα x PPARγ x DPP-4 相关的专利（医药）

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项与 PPARα x PPARγ x DPP-4 相关的文献（医药）

2024-12-01·Computational Biology and Chemistry

Mechanistic insights into antidiabetic potential of Ficus viren against multi organ specific diabetic targets: molecular docking, MDS, MM-GBSA analysis

Article

作者: Sharma, Sachin ; Sharma, Onkar ; Choudhary, Manjusha ; Injeti, Elisha ; Mittal, Ashwani

Ficus viren has been traditionally used to treat diabetes, and its extract inhibits carbohydrate/lipid metabolism and possesses anti-hyperglycemic potential. However, there is conflicting investigation related to F. viren extract effect on carbohydrate metabolism. Thus, bioactive and mechanism behind its antidiabetic potential is still scanty. This study explored F. viren's anti-diabetic property by identifying potential phytoconstituents and mechanism. A sequential in-silico approach was used i.e., druglikeness, molecular docking, post-docking MM-GBSA, ADMET studies, molecular dynamic simulation (MDS), and post-MDS MM-GBSA. We screened ∼32 phytoconstituents and twelve potential organ-specific diabetic targets (O.S.D.Ts i.e., IR, DPP-4, ppar-γ, ppar-α, ppar-δ, GLP-1R, SIRT-1, AMPK, GSK-3β, RAGE, and AR). Drug likeness study identified 18 druggable candidates among 32 phytoconstituents. K3A, quercetin, scutellarein, sorbifolin, and vogeline J identified as potential ligands from druggable ligands, using IR as the standard target. Subsequently, potential ligands docked with remaining O.S.D.Ts. and data showed that K3A binds strongly with AMPK, ppar-δ, DPP-4, and GSK-3β, while scutellarein binds with AR and ppar-α. Sorbifolin, quercetin, and vogeline J binds with ppar-α, ppar-γ, and RAGE, respectively. Post-docking MM-GBSA data (∆G_Bind) also depicted potential ligand's strong binding affinities with their corresponding targets. Thereafter, simulation data revealed that only scutellarein and sorbifolin showed dynamic stability with their respective targets, i.e., AR/ppar-α and ppar-α, respectively. Interestingly, post-MDS MM-GBSA revealed that only scutellarein exhibited strong ∆G_Bind of -55.08 kcal/mol and -75.48 kcal/mol with AR and ppar-α, respectively. Though, collective computational analysis supports antidiabetic potential of F. viren through AR and ppar-α modulation by scutellarein.

2024-08-01·Archives of Biochemistry and Biophysics

Research into how carvacrol and metformin affect several human proteins in a hyperglycemic condition: A comparative study in silico and in vitro

Article

作者: Beker, Merve ; Pérez-Sánchez, Horacio ; Sarikamis, Bahar ; Kalkan Cakmak, Rabia ; Ercin, Nilufer ; Carmena-Bargueño, Miguel ; Kilic, Ulkan ; Yenmis, Guven ; Besli, Nail

Carvacrol (CV) is an organic compound found in the essential oils of many aromatic herbs. It is nearly unfeasible to analyze all the current human proteins for a query ligand using in vitro and in vivo methods. This study aimed to clarify whether CV possesses an anti-diabetic feature via Docking-based inverse docking and molecular dynamic (MD) simulation and in vitro characterization against a set of novel human protein targets. Herein, the best poses of CV docking simulations according to binding energy ranged from -7.9 to -3.5 (kcal/mol). After pathway analysis of the protein list through GeneMANIA and WebGestalt, eight interacting proteins (DPP4, FBP1, GCK, HSD11β1, INSR, PYGL, PPARA, and PPARG) with CV were determined, and these proteins exhibited stable structures during the MD process with CV. In vitro application, statistically significant results were achieved only in combined doses with CV or metformin. Considering all these findings, PPARG and INSR, among these target proteins of CV, are FDA-approved targets for treating diabetes. Therefore, CV may be on its way to becoming a promising therapeutic compound for treating Diabetes Mellitus (DM). Our outcomes expose formerly unexplored potential target human proteins, whose association with diabetic disorders might guide new potential treatments for DM.

Scientific Reports

Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia–reperfusion injury in diabetes mellitus rats

Article

作者: Wang, Lian ; Li, Wenyuan ; Wang, Yao ; Xu, Heng

AbstractDapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut microbiota through the metabolic conversion of choline and phosphatidylcholine. Ferroptosis may offer novel therapeutic avenues for the management of diabetes and myocardial ischemia–reperfusion injury (IRI). However, the precise mechanism underlying ferroptosis in cardiomyocytes and the specific role of TMAO generated by gut microbiota in the therapeutic approach for DM and myocardial IRI utilizing DAPA need to be further explored. Nine male SD rats with specific pathogen-free (SPF) status were randomly divided equally into the normal group, the DM + IRI (DIR) group, and the DAPA group. The diversity of the gut microbiota was analyzed using 16S rRNA gene sequencing. Additionally, the Wekell technique was employed to measure the levels of TMAO in the three groups. Application of network pharmacology to search for intersection targets of DAPA, DIR, and ferroptosis, and RT-PCR experimental verification. Ultimately, the overlapping targets that were acquired were subjected to molecular docking analysis with TMAO. The changes of Bacteroidetes and Firmicutes in the gut microbiota of DIR rats were most significantly affected by DAPA. Escherichia-Shigella and Prevotella_9 within the phylum Bacteroidetes could be identified as the primary effects of DAPA on DIR. Compared with the normal group, the TMAO content in the DIR group was significantly increased, while the TMAO content in the DAPA group was decreased compared to the DIR group. For the network pharmacology analysis, DAPA and DIR generated 43 intersecting target genes, and then further intersected with ferroptosis-related genes, resulting in 11 overlapping target genes. The mRNA expression of ALB, HMOX1, PPARG, CBS, LCN2, and PPARA decreased in the DIR group through reverse transcription polymerase chain reaction (RT-PCR) validation, while the opposite trend was observed in the DAPA group. The docking score between TMAO and DPP4 was − 5.44, and the MM-GBSA result of − 22.02 kcal/mol. It epitomizes the finest docking performance among all the target genes with the lowest score. DAPA could reduce the levels of metabolite TMAO produced by gut microbiota, thereby regulating related target genes to decrease ferroptosis in DIR cardiomyocytes.