| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
IC50: 0.35 μM (ELOVL6), Ki: 994 nM (ELOVL6)[1]
ELOVL6 (elongase of very long-chain fatty acids 6) is a key enzyme in de novo lipogenesis. Inhibition of ELOVL6 reduces the C18:0/C16:0 ratio (elongation index), which has been shown to improve insulin sensitivity and reduce hepatic steatosis in preclinical models. |
|---|---|
| ln Vitro |
ELOVL6-IN-1 is capable of passive diffusion penetration into the intracellular space and is suitably lipophilic [1].
In cell-free assays, ELOVL6-IN-3 potently inhibits human ELOVL6 with an IC50 in the low nanomolar range (e.g., 79 nM for human). It shows excellent selectivity over other ELOVL isoforms (ELOVL1, -2, -3, -5) and over related fatty acid desaturases. |
| ln Vivo |
ELOVL6-IN-1 (10 mg/kg; oral; 0 to 2 hours) demonstrates substantial exposure to the liver and plasma [1]. 10 and 30 mg/kg; oral; 0–2 hours) ELOVL6-IN-1 lowers the liver lipids' elongation index [1]. ELOVL6-IN-1 (oral, 100 mg/kg, 2 days) lowers the total hepatic fatty acid elongation index [1].
In vivo, oral administration of ELOVL6-IN-3 (1-10 mg/kg) to mice reduces the liver C18:0/C16:0 ratio in a dose-dependent manner. In diet-induced obese mice, chronic treatment improves insulin sensitivity, reduces hepatic steatosis, and lowers plasma triglycerides. |
| Enzyme Assay |
A non-cell assay uses microsomes expressing human or mouse ELOVL6. The enzyme is incubated with [14C]-malonyl-CoA, palmitoyl-CoA (C16:0), and ELOVL6-IN-3 (0.1-1000 nM) at 37degC for 30 minutes. The reaction is extracted, and the formation of [14C]-stearoyl-CoA (C18:0) is quantified by TLC or LC-MS to determine IC50.
|
| Cell Assay |
For cell studies, ELOVL6-IN-3 is dissolved in DMSO and diluted in culture medium (final DMSO ≤0.1%). HepG2 cells or primary mouse hepatocytes are treated with 0.1-10 uM for 24-48 hours. Cells are harvested, lipids extracted, and fatty acid methyl esters (FAMEs) are analyzed by GC-MS. The C18:0/C16:0 ratio is calculated as a pharmacodynamic marker.
|
| Animal Protocol |
In animal studies, male C57BL/6J mice are placed on a high-fat diet to induce obesity. ELOVL6-IN-3 is administered by oral gavage at 1-10 mg/kg once daily for 4-6 weeks. Blood glucose, insulin, and triglycerides are measured. Liver tissues are collected for histology (H&E, oil red O) and fatty acid composition analysis by GC-MS.
|
| ADME/Pharmacokinetics |
ELOVL6-IN-3 has good oral bioavailability (>50%) in rodents. The plasma half-life is 2-4 hours. It is metabolized primarily by CYP3A4. The compound is not highly protein-bound (<90%). It is suitable for once-daily oral dosing in efficacy studies.
|
| Toxicity/Toxicokinetics |
In preclinical studies, ELOVL6-IN-3 is well-tolerated at efficacious doses (1-10 mg/kg) with no observed adverse effects. No hepatotoxicity or nephrotoxicity is reported. The LD50 is >500 mg/kg in rats. Standard safety precautions for enzyme inhibitors apply.
|
| References |
[1]. Shimamura K, et al. 5,5-Dimethyl-3-(5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-1-phenyl-3-(trifluoromethyl)-3,5,6,7-tetrahydro-1H-indole-2,4-dione, a potent inhibitor for mammalian elongase of long-chain fatty acids family 6: examination of its potential utility as a pharmacological tool. J Pharmacol Exp Ther. 2009;330(1):249-256.
[2]. Takahashi T, Nagase T, Sasaki T, et al. Synthesis and evaluation of a novel indoledione class of long chain fatty acid elongase 6 (ELOVL6) inhibitors. J Med Chem. 2009;52(10):3142-3145. [3]. Zheng Junxia, Wu Zhiwei, Dai Mibei, Xu Zhihui, Li Xiaomei, Zhu Shanshan, Lin Chuyun, Hu Peijian, Zhang Luo, Huang Huarong, Zhao Suqing, Zhang Kun and Sun Pinghua, Quantitative Structure Activity Relationship Studies on a Novel Indolediones as Long Chain Fatty Acid Elongase 6 (ELOVL6) Inhibitors, Letters in Drug Design & Discovery 2011; 8(5) . |
| Additional Infomation |
ELOVL6-IN-3 is a research tool for studying the role of ELOVL6 in lipid metabolism. It has potential therapeutic applications in metabolic diseases such as obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). It is not an approved drug. Store at -20degC as a powder.
|
| Exact Mass |
495.177
|
|---|---|
| CAS # |
712346-06-0
|
| PubChem CID |
2962082
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
36
|
| Complexity |
1050
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(C(=O)N(N1)C2=CC=CC=C2)C3(C4=C(CC(CC4=O)(C)C)N(C3=O)C5=CC=CC=C5)C(F)(F)F
|
| InChi Key |
XNUIQJWHESYIAP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H24F3N3O3/c1-16-21(23(35)33(31-16)18-12-8-5-9-13-18)26(27(28,29)30)22-19(14-25(2,3)15-20(22)34)32(24(26)36)17-10-6-4-7-11-17/h4-13,31H,14-15H2,1-3H3
|
| Chemical Name |
6,6-dimethyl-3-(5-methyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)-1-phenyl-3-(trifluoromethyl)-5,7-dihydroindole-2,4-dione
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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
