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.

Start Date24 Feb 2020

Sponsor / Collaborator

Chong Kun Dang Pharmaceutical Corp.

NCT03499704 / Active, not recruitingPhase 4

A Multicenter, Randomized, Open-label, Two-arm, Phase 4 Study to Evaluate the Effect of Add-on Pioglitazone or Dapagliflozin in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled by Dipeptidyl Peptidase-4 Inhibitor and Metformin Therapy

The purpose of this study is to assess the pioglitazone plus alogliptin plus metformin is non-inferior to dapagliflozin plus alogliptin plus metformin on glycosylated haemoglobin (HbA1c) change from baseline at Week 26.

Start Date11 Feb 2020

Sponsor / Collaborator

Celltrion Pharm Inc.

100 Clinical Results associated with PPARγ x DPP-4

100 Translational Medicine associated with PPARγ x DPP-4

0 Patents (Medical) associated with PPARγ x DPP-4

Literatures (Medical) associated with PPARγ x DPP-4

01 Dec 2024·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

Author: 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.

01 Aug 2024·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

Author: 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.

31 May 2024·The FASEB Journal

Dipeptidyl peptidase‐4 disturbs adipocyte differentiation via the negative regulation of the glucagon‐like peptide‐1/adiponectin‐cathepsin K axis in mice under chronic stress conditions

Article

Author: Shu, Shangzhi ; Li, Ping ; Hong, Lan ; Zhao, Longguo ; Kim, Weon ; Kuzuya, Masafumi ; Piao, Jinshun ; Yue, Xueling ; Xu, Shengnan ; Zhang, Meiping ; Liu, Bin ; Cheng, Xian Wu

AbstractExposure to chronic psychosocial stress is a risk factor for metabolic disorders. Because dipeptidyl peptidase‐4 (DPP4) and cysteinyl cathepsin K (CTSK) play important roles in human pathobiology, we investigated the role(s) of DPP4 in stress‐related adipocyte differentiation, with a focus on the glucagon‐like peptide‐1 (GLP‐1)/adiponectin‐CTSK axis in vivo and in vitro. Plasma and inguinal adipose tissue from non‐stress wild‐type (DPP4+/+), DPP4‐knockout (DPP4−/−) and CTSK‐knockout (CTSK−/−) mice, and stressed DPP4+/+, DPP4−/−, CTSK−/−, and DPP4+/+ mice underwent stress exposure plus GLP‐1 receptor agonist exenatide loading for 2 weeks and then were analyzed for stress‐related biological and/or morphological alterations. On day 14 under chronic stress, stress decreased the weights of adipose tissue and resulted in harmful changes in the plasma levels of DPP4, GLP‐1, CTSK, adiponectin, and tumor necrosis factor‐α proteins and the adipose tissue levels of CTSK, preadipocyte factor‐1, fatty acid binding protein‐4, CCAAT/enhancer binding protein‐α, GLP‐1 receptor, peroxisome proliferator‐activated receptor‐γ, perilipin2, secreted frizzled‐related protein‐4, Wnt5α, Wnt11 and β‐catenin proteins and/or mRNAs as well as macrophage infiltration in adipose tissue; these changes were rectified by DPP4 deletion. GLP‐1 receptor activation and CTSK deletion mimic the adipose benefits of DPP4 deficiency. In vitro, CTSK silencing and overexpression respectively prevented and facilitated stress serum and oxidative stress‐induced adipocyte differentiation accompanied with changes in the levels of pref‐1, C/EBP‐α, and PPAR‐γ in 3T3‐L1 cells. Thus, these findings indicated that increased DPP4 plays an essential role in stress‐related adipocyte differentiation, possibly through a negative regulation of GLP‐1/adiponectin‐CTSK axis activation in mice under chronic stress conditions.

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