L-165041PPARβ/δ agonist,cell permeable,potent and selective CAS# 79558-09-1 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 79558-09-1 | SDF | Download SDF |
PubChem ID | 6603901 | Appearance | Powder |
Formula | C22H26O7 | M.Wt | 402.44 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : 50 mg/mL (124.24 mM; Need ultrasonic) H2O : < 0.1 mg/mL (insoluble) | ||
Chemical Name | 2-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid | ||
SMILES | CCCC1=C(C=CC(=C1O)C(=O)C)OCCCOC2=CC=C(C=C2)OCC(=O)O | ||
Standard InChIKey | HBBVCKCCQCQCTJ-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C22H26O7/c1-3-5-19-20(11-10-18(15(2)23)22(19)26)28-13-4-12-27-16-6-8-17(9-7-16)29-14-21(24)25/h6-11,26H,3-5,12-14H2,1-2H3,(H,24,25) | ||
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. |
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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. |
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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. |
Description | L-165041 is a potent agonist of PPARδ with Ki value of 6 nM. | |||||
Targets | PPARδ | |||||
IC50 | 6 nM (Ki) |
L-165041 Dilution Calculator
L-165041 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.4848 mL | 12.4242 mL | 24.8484 mL | 49.6968 mL | 62.1211 mL |
5 mM | 0.497 mL | 2.4848 mL | 4.9697 mL | 9.9394 mL | 12.4242 mL |
10 mM | 0.2485 mL | 1.2424 mL | 2.4848 mL | 4.9697 mL | 6.2121 mL |
50 mM | 0.0497 mL | 0.2485 mL | 0.497 mL | 0.9939 mL | 1.2424 mL |
100 mM | 0.0248 mL | 0.1242 mL | 0.2485 mL | 0.497 mL | 0.6212 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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Ki: 6 nM for PPARγ
Peroxisome proliferator-activated receptor (PPARγ) is known to be expressed ubiquitously and involved in lipid and glucose metabolism. Studies have demonstrated that PPARγ is expressed in endothelial cells and plays a potential role in endothelial proliferation and survival. L-165041 is reported as a selective and potent PPARγ ligand.
In vitro: L-165041, which is a selective and potent PPARδligand, displayed in this specified transactivation system, apart from its highly efficacious PPARδ agonist activity, partial and full agonism at, respectively, PPARγ2 and PPARαsubtypes [1].
In vivo: L-165041 could drastically reduce lipid accumulation in the mouse liver, decreasing total hepatic triglyceride and cholesterol content compared to the vehicle group. Gene analysis demonstrated that L-165041 lowered hepatic expression of PPARγ, apolipoprotein B, IL-1β, and interleukin-6. In contrast, L-165041 increased hepatic expressions of PPARδ, lipoprotein lipase, and ATP-binding cassette transporter G1 (ABCG1) [2].
Clinical trial: Up to now, L-165041 is still in the preclinical development stage.
Reference:
[1] Wurch T, Junquero D, Delhon A, Pauwels J. Pharmacological analysis of wild-type alpha, gamma and delta subtypes of the human peroxisome proliferator-activated receptor. Naunyn Schmiedebergs Arch Pharmacol. 2002 Feb;365(2):133-40.
[2] Lim HJ, Park JH, Lee S, Choi HE, Lee KS, Park HY. PPARdelta ligand L-165041 ameliorates Western diet-induced hepatic lipid accumulation and inflammation in LDLR-/- mice. Eur J Pharmacol. 2009 Nov 10;622(1-3):45-51.
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PPAR delta agonist L-165041 inhibits rat vascular smooth muscle cell proliferation and migration via inhibition of cell cycle.[Pubmed:18585719]
Atherosclerosis. 2009 Feb;202(2):446-54.
The peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors consists of three subtypes (alpha, beta/delta, and gamma). PPAR delta is ubiquitously expressed and involved in lipid and glucose metabolism. However, the effect of PPAR delta on vascular smooth muscle cell (VSMC) proliferation and migration has not been fully elucidated yet. Here, we investigated the effect of L-165041, a selective ligand for PPAR delta, on PDGF-induced rat VSMC proliferation. Our data show that L-165041 inhibited rat VSMC proliferation in a dose dependent manner by blocking G(1) to S phase progression and repressing the phosphorylation of retinoblastoma protein (Rb). Furthermore, L-165041 inhibited PDGF-induced expression of cyclin D1 and CDK4. These effects less likely involve PPAR gamma pathway because PPAR gamma antagonist GW9662 pretreatment failed to reverse the inhibitory effect of L-165041 on rVSMC proliferation and migration. For in vivo studies, L-165041 was administered to Sprague-Dawley rats using osmotic pumps before and after the carotid balloon injury, and L-165041 decreased neointima formation after the carotid injury. In conclusion, our results suggest that PPAR delta ligand L-165041 can be a therapeutic agent to control pathologic cardiovascular conditions such as restenosis and atherosclerosis.
The PPARbeta agonist L-165041 promotes VEGF mRNA stabilization in HPV18-harboring HeLa cells through a receptor-independent mechanism.[Pubmed:24172859]
Cell Signal. 2014 Feb;26(2):433-43.
Peroxisome Proliferator-Activated Receptor-beta (PPARbeta) is a ligand-inducible transcription factor activated by both natural (fatty acids and derivatives) and high affinity synthetic agonists. It is thought to play a role in angiogenesis development and Vascular Endothelial Growth Factor (VEGF) regulation but its contribution remains unclear. Until now, the PPARbeta agonism effect on VEGF expression in cervical cancer cells was unknown. This led to our interest in assessing the effect of PPARbeta activation on the regulation of different VEGF isoforms mRNA expression and the impact of E6 viral oncoprotein and its target p53 on this regulation in cervical cancer cells. Here, we showed that the PPARbeta agonist L-165041 induces VEGF(121), VEGF(165) and VEGF(189) expression in HPV (Human Papillomavirus) positive HeLa cells but not in HPV negative cells. The underlying mechanisms did involve neither E6 oncoprotein nor p53. We highlighted a novel mode of PPARbeta ligand action including a post-transcriptional regulation of VEGF mRNA expression through the p38 MAPK signaling pathway and the activation of the mRNA-stabilizing factor HuR. But most importantly, we clearly demonstrated that L-165041 acts independently of PPARbeta since its effect was not reversed by a chemical inhibition with a specific antagonist and the siRNA-mediated knockdown of the nuclear receptor. As VEGF is crucial for cancer development, the impact of PPARbeta ligands on VEGF production is of high importance. Thus, the molecular mechanism of their action has to be elucidated and as a result, PPARbeta agonists currently in clinical trials should be carefully monitored.
PPARdelta ligand L-165041 ameliorates Western diet-induced hepatic lipid accumulation and inflammation in LDLR-/- mice.[Pubmed:19766624]
Eur J Pharmacol. 2009 Nov 10;622(1-3):45-51.
Although peroxisome proliferator-activated receptor delta (PPARdelta) has been implicated in energy metabolism and lipid oxidation process, detailed roles of PPARdelta in lipid homeostasis under pathologic conditions still remain controversial. Thus, we investigated the effect of PPARdelta ligand L-165041 on Western diet-induced fatty liver using low-density lipoprotein receptor-deficient (LDLR(-/-)) mice. LDLR(-/-) mice received either L-165041 (5mg/kg/day) or vehicle (0.1N NaOH) with Western diet for 16 weeks. According to our data, L-165041 drastically reduced lipid accumulation in the liver, decreasing total hepatic cholesterol and triglyceride content compared to the vehicle group. Gene expression analysis demonstrated that L-165041 lowered hepatic expression of PPARgamma, apolipoprotein B, interleukin 1 beta (IL-1beta), and interleukin-6. In contrast, L-165041 increased hepatic expressions of PPARdelta, lipoprotein lipase (LPL), and ATP-binding cassette transporter G1 (ABCG1). Our data suggest that L-165041 might be effective in preventing Western diet-induced hepatic steatosis by regulating genes involved in lipid metabolism and the inflammatory response.
The PPARdelta ligand L-165041 inhibits VEGF-induced angiogenesis, but the antiangiogenic effect is not related to PPARdelta.[Pubmed:22234939]
J Cell Biochem. 2012 Jun;113(6):1947-54.
Peroxisome proliferator-activated receptor (PPAR)delta is known to be expressed ubiquitously and involved in lipid and glucose metabolism. Recent studies have demonstrated that PPARdelta is expressed in endothelial cells (ECs) and plays a potential role in endothelial survival and proliferation. Although PPARalpha and PPARgamma are well recognized to play anti-inflammatory, antiproliferative, and antiangiogenic roles in ECs, the general effect of PPARdelta on angiogenesis in ECs remains unclear. Thus, we investigated the effect of the PPARdelta ligand L-165041 on vascular EC proliferation and angiogenesis in vitro as well as in vivo. Our data show that L-165041 inhibited VEGF-induced cell proliferation and migration in human umbilical vein ECs (HUVECs). L-165041 also inhibited angiogenesis in the Matrigel plug assay and aortic ring assay. Flow cytometric analysis indicated that L-165041 reduced the number of ECs in the S phase and the expression levels of cell cycle regulatory proteins such as cyclin A, cyclin E, CDK2, and CDK4; phosphorylation of the retinoblastoma protein was suppressed by pretreatment with L-165041. We confirmed whether these antiangiogenic effects of L-165041 were PPARdelta-dependent using GW501516 and PPARdelta siRNA. GW501516 treatment did not inhibit VEGF-induced angiogenesis, and transfection of PPARdelta siRNA did not reverse this antiangiogenic effect of L-165041, suggesting that the antiangiogenic effect of L-165041 on ECs is PPARdelta-independent. Together, these data indicate that the PPARdelta ligand L-165041 inhibits VEGF-stimulated angiogenesis by suppressing the cell cycle progression independently of PPARdelta. This study highlights the therapeutic potential of L-165041 in the treatment of many disorders related to pathological angiogenesis.