| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
L-165041 is a novel and potent agonist of the nuclear receptor PPARβ/δ that induces adipocyte differentiation in NIH-PPARδ cells. It activates PPARδ and PPARγ with Kis of 6 nM and appr 730 nM, respectively.
| Targets |
PPARδ(Ki = 6 nM); PPARγ (Ki = 730 nM)
|
|---|---|
| ln Vitro |
PPARδ agonist L-165041 has a Ki of 6 nM for PPARδ and roughly 730 nM for PPARγ [1]. L-165041 (1 or 5 μM) prevents endothelial cell (EC) migration and rotation caused by VEGF. L-165041 has a deleterious effect on the VEGF-activated human venovenous endothelial cells' (HUVEC) cell cycle progression. PPARδ-uncoupled, VEGF-induced angiogenesis is inhibited by L-165041 (10 μM) [2]. rVSMC migration and PDGF-induced migration are inhibited by PPARδ ligand L-165041. After an hour, PDGF-induced cell migration was reduced by L-165041. Significant inhibition of PDGF-induced S phase transition is seen with 10 μM L-165041 [4].
|
| ln Vivo |
In mice, L-165041 (5 mg/kg/day, i.p.) dramatically lowers the production of lipid droplets. L-165041 dramatically lowered the mice's triglyceride levels. L-165041 went up in contrast to the vector group. mice given L-165041 treatment while the vehicle group's lipoprotein lipase (LPL) expression was significantly elevated [3].
|
| Enzyme Assay |
Peroxisome proliferator-activated receptor (PPAR)δ is known to be expressed ubiquitously and involved in lipid and glucose metabolism. Recent studies have demonstrated that PPARδ is expressed in endothelial cells (ECs) and plays a potential role in endothelial survival and proliferation. Although PPARα and PPARγ are well recognized to play anti-inflammatory, antiproliferative, and antiangiogenic roles in ECs, the general effect of PPARδ on angiogenesis in ECs remains unclear. Thus, we investigated the effect of the PPARδ 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 PPARδ-dependent using GW501516 and PPARδ siRNA. GW501516 treatment did not inhibit VEGF-induced angiogenesis, and transfection of PPARδ siRNA did not reverse this antiangiogenic effect of L-165041, suggesting that the antiangiogenic effect of L-165041 on ECs is PPARδ-independent. Together, these data indicate that the PPARδ ligand L-165041 inhibits VEGF-stimulated angiogenesis by suppressing the cell cycle progression independently of PPARδ. This study highlights the therapeutic potential of L-165041 in the treatment of many disorders related to pathological angiogenesis[3].
|
| Cell Assay |
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[4].
|
| Animal Protocol |
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[3].
|
| References |
|
| Additional Infomation |
2-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid is an aromatic ketone.
|
| Molecular Formula |
C22H26O7
|
|---|---|
| Molecular Weight |
402.443
|
| Exact Mass |
402.167
|
| Elemental Analysis |
C, 65.66; H, 6.51; O, 27.83
|
| CAS # |
79558-09-1
|
| PubChem CID |
6603901
|
| Appearance |
Typically exists as White to off-white solids at room temperature
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
600.8±55.0 °C at 760 mmHg
|
| Melting Point |
127-128ºC(lit.)
|
| Flash Point |
206.5±25.0 °C
|
| Vapour Pressure |
0.0±1.8 mmHg at 25°C
|
| Index of Refraction |
1.566
|
| LogP |
4.98
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
29
|
| Complexity |
501
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(COC1C=CC(OCCCOC2C(CCC)=C(O)C(C(C)=O)=CC=2)=CC=1)O
|
| InChi Key |
HBBVCKCCQCQCTJ-UHFFFAOYSA-N
|
| InChi Code |
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)
|
| Chemical Name |
2-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid
|
| Synonyms |
L 165041; L165041; L-165041; L-165,041; 2-(4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy)phenoxy)acetic acid; L165041; 2-(4-(3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-propoxy)phenoxy)acetic acid; 2-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid; Aceticacid, 2-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]-; L-165041
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~124.24 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4848 mL | 12.4242 mL | 24.8484 mL | |
| 5 mM | 0.4970 mL | 2.4848 mL | 4.9697 mL | |
| 10 mM | 0.2485 mL | 1.2424 mL | 2.4848 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
