ZLN005

transcriptional regulator of PGC-1α CAS# 49671-76-3

ZLN005

Catalog No. BCC4882----Order now to get a substantial discount!

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Chemical structure

ZLN005

3D structure

Chemical Properties of ZLN005

Cas No. 49671-76-3 SDF Download SDF
PubChem ID 899323 Appearance Powder
Formula C17H18N2 M.Wt 250.34
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : 22 mg/mL (87.88 mM; Need ultrasonic)
Chemical Name 2-(4-tert-butylphenyl)-1H-benzimidazole
SMILES CC(C)(C)C1=CC=C(C=C1)C2=NC3=CC=CC=C3N2
Standard InChIKey LQUNNCQSFFKSSK-UHFFFAOYSA-N
Standard InChI InChI=1S/C17H18N2/c1-17(2,3)13-10-8-12(9-11-13)16-18-14-6-4-5-7-15(14)19-16/h4-11H,1-3H3,(H,18,19)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of ZLN005

DescriptionZLN005 is a novel transcriptional regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). IC50 value: Target: PGC-1α in vitro: ZLN005 increases expression of the PGC-1α gene in L6 myotubes. ZLN005 increased PGC-1α mRNA levels in a dose-dependent manner; 20 μmol/L ZLN005 caused a threefold increase over the control after 24 h. At 10 μmol/L, the PGC-1α mRNA levels were increased to almost the same extent at 16 to 48 h [1]. ZLN005 did not increase the expression of the PGC-1α gene in rat primary hepatocytes. AMP-activated protein kinase is involved in the mechanism inducing PGC-1α in L6 myotubes [1] in vivo: An insulin tolerance test revealed that treatment with ZLN005 significantly decreased insulin resistance in db/db mice, as evidenced by the approximately 18% decrease in the AUC. A PTT also was performed in db/db mice, and ZLN005 improved pyruvate tolerance, as evidenced by the 16% decrease in the AUC. In db/db mice, plasma NEFA and triglyceride levels were decreased by 20% and 37%, respectively, and cholesterol was decreased by 10% with ZLN005 treatment. Plasma insulin and β-hydroxybutyrate content, liver/bodyweight index and adipose composition, and muscle and liver triglyceride levels, however, were not ameliorated by treatment with ZLN005 or metformin [1].

References:
[1]. Zhang LN, et al. Novel small-molecule PGC-1α transcriptional regulator with beneficial effects on diabetic db/db mice. Diabetes. 2013 Apr;62(4):1297-307.

ZLN005 Dilution Calculator

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ZLN005 Molarity Calculator

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Preparing Stock Solutions of ZLN005

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.9946 mL 19.9728 mL 39.9457 mL 79.8913 mL 99.8642 mL
5 mM 0.7989 mL 3.9946 mL 7.9891 mL 15.9783 mL 19.9728 mL
10 mM 0.3995 mL 1.9973 mL 3.9946 mL 7.9891 mL 9.9864 mL
50 mM 0.0799 mL 0.3995 mL 0.7989 mL 1.5978 mL 1.9973 mL
100 mM 0.0399 mL 0.1997 mL 0.3995 mL 0.7989 mL 0.9986 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on ZLN005

ZLN005 is a novel transcriptional regulator of PGC-1α [1].

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is an inducible coregulator that regulates energy metabolism. PGC-1α regulates glucose and fatty acid metabolism, mitochondrial biogenesis and so on. Dysregulation of PGC-1α is correlated with insulin resistance and type 2 diabetes mellitus [1].

ZLN005 is a novel PGC-1α transcriptional regulator. In the PGC-1α promoter reporter assay, ZLN005 potently inhibited luciferases. In L6 myotubes, ZLN005 dose-dependently increased PGC-1α mRNA levels. ZLN005 (10 μM) increased the mRNA levels of cytochrome c oxidase 5b (cox5b), acyl-CoA oxidase, strogen-related receptor α (ERRα), NRF1 and GLUT4. ZLN005 (20 μM) increased glucose uptake and oxidation of palmitic acid by 1.8-fold and 1.28-fold respectively in a dose dependent way. In L6 myotubes transfected with PGC-1α siRNA, ZLN005-stimulated oxidation of palmitic acid and expression of the PGC-1α gene was blocked. In L6 myotubes, ZLN005 increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) [1].

In db/db mice, ZLN005 reduced RER, suggesting a shift to fatty acid use. ZLN005 significantly reduced fasting blood glucose and random blood glucose levels. Also, ZLN005 improved glucose clearance and pyruvate tolerance and reduced insulin resistance [1].

Reference:
[1].  Zhang LN, Zhou HY, Fu YY, et al. Novel Small-Molecule PGC-1a Transcriptional Regulator With Beneficial Effects on Diabetic db/db Mice. Diabetes, 2013, 62(4): 1297-1307.

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References on ZLN005

ZLN005 protects cardiomyocytes against high glucose-induced cytotoxicity by promoting SIRT1 expression and autophagy.[Pubmed:27208585]

Exp Cell Res. 2016 Jul 1;345(1):25-36.

Diabetic cardiomyopathy increases the risk for the development of heart failure independent of coronary artery disease and hypertension. Either type 1 or type 2 diabetes is often accompanied by varying degrees of hyperglycemia, which has been proven to induce myocardial apoptosis in animal models. Recently, a novel small molecule, ZLN005, has been reported to show antidiabetic efficacy in a mouse model, possibly by induction of PGC-1alpha expression. In this study, we investigated whether ZLN005 protects cardiomyocytes against high glucose-induced cytotoxicity and the mechanisms involved. Neonatal mouse cardiomyocytes were incubated with media containing 5.5 or 33mM glucose for 24h in the presence or absence of ZLN005. ZLN005 treatment led to ameliorated cardiomyocyte oxidative injury, enhanced cell viability, and reduced apoptosis in the high glucose environment. Western blot analysis revealed that high glucose suppressed cardiomyocyte autophagy, whereas ZLN005 increased the expression of autophagy marker proteins ATG5, beclin1, and LC3 II/LC3 I; this increase was accompanied by increased expression of SIRT1. Furthermore, EX527, a SIRT1-specific inhibitor, weakened the protective effects of ZLN005 on cardiomyocytes subjected to high glucose. Taken together, these results suggest that ZLN005 suppresses high glucose-induced cardiomyocyte injury by promoting SIRT1 expression and autophagy.

Description

ZLN005 is a potent activator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).

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