| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
CYP4A11 19 nM (IC50) CYP4F2 17 nM (IC50)
Cytochrome P450 (CYP) 4A11 and CYP4F2. CYP4A11/CYP4F2-IN-1 is a potent dual inhibitor of these enzymes, with IC50 values of 19 nM for CYP4A11 and 17 nM for CYP4F2. These CYP enzymes are responsible for the synthesis of 20-HETE from arachidonic acid. By inhibiting CYP4A11 and CYP4F2, the compound reduces 20-HETE production, thereby modulating vascular and renal function. |
|---|---|
| ln Vitro |
In human renal microsomes, CYP4A11/CYP4F2-IN-1 (compound 2) suppresses the synthesis of 20-Hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid, with an IC50 of 4.2 nM[1].
CYP4A11/CYP4F2-IN-1 inhibits CYP4A11 with an IC50 of 19 nM and CYP4F2 with an IC50 of 17 nM. It demonstrates a 7.4-fold higher potency for CYP4A11 inhibition compared to compound 11c (CYP4A11/CYP4F2-IN-2). The compound's potent inhibition of these enzymes reduces 20-HETE production, with implications for vascular tone and renal function. |
| ln Vivo |
In vivo, CYP4A11/CYP4F2-IN-1 has potential for the research of renal diseases and cardiovascular and cerebrovascular diseases. By inhibiting CYP4A11 and CYP4F2 and reducing 20-HETE production, the compound may modulate blood pressure, kidney function, and metabolic processes. Its effects would be assessed in animal models of hypertension, renal dysfunction, and metabolic disorders.
|
| Enzyme Assay |
In vitro enzyme activity assays for CYP4A11/CYP4F2-IN-1 involve measuring its ability to inhibit CYP4A11 and CYP4F2 enzymatic activity. Recombinant human CYP4A11 and CYP4F2 enzymes are incubated with arachidonic acid substrate in the presence of increasing concentrations of the compound. The production of 20-HETE is measured by LC-MS/MS, and IC50 values are determined from dose-response curves.
|
| Cell Assay |
In vitro cellular assays for CYP4A11/CYP4F2-IN-1 involve treating renal or vascular cells with the compound and measuring its effects on 20-HETE production and downstream signaling pathways. Cells are stimulated with appropriate agonists, and 20-HETE levels are measured by LC-MS/MS. The compound's effects on cell proliferation, inflammation, and vascular tone can also be assessed in relevant cell types.
|
| Animal Protocol |
In vivo efficacy of CYP4A11/CYP4F2-IN-1 would be evaluated in animal models of hypertension, kidney disease, and metabolic disorders. The compound could be administered orally or via injection. Efficacy endpoints would include blood pressure, renal function parameters, 20-HETE levels, and markers of inflammation and oxidative stress.
|
| ADME/Pharmacokinetics |
CYP4A11/CYP4F2-IN-1 has a molecular formula of C16H20N4O2 and a molecular weight of 300.36. As a small-molecule CYP inhibitor, its pharmacokinetic properties would be characteristic of this class. The compound is supplied for research use only. Detailed PK parameters are not extensively reported in the available literature.
|
| Toxicity/Toxicokinetics |
No specific toxicity data is available for CYP4A11/CYP4F2-IN-1 in the provided literature. As a research compound, its safety profile would be an important consideration for in vivo applications. Potential toxicities could be related to its effects on 20-HETE production and CYP enzyme inhibition in various tissues. Standard preclinical safety studies would be required.
|
| References |
[1]. Kawamura M, et, al. Discovery of Novel Pyrazolylpyridine Derivatives for 20-Hydroxyeicosatetraenoic Acid Synthase Inhibitors with Selective CYP4A11/4F2 Inhibition. J Med Chem. 2022 Nov 10;65(21):14599-14613.
|
| Additional Infomation |
CYP4A11/CYP4F2-IN-1 is a potent dual inhibitor of cytochrome P450 (CYP) 4A11 and CYP4F2, with IC50 values of 19 nM and 17 nM, respectively. It has potential for the research of kidney diseases, cardiovascular diseases, and cerebrovascular diseases. The compound is a research tool for studying the role of 20-HETE in physiology and disease. It is not approved for clinical use.
|
| Molecular Formula |
C15H15N3OS
|
|---|---|
| Molecular Weight |
285.3641
|
| Exact Mass |
285.093
|
| CAS # |
502654-40-2
|
| PubChem CID |
86214066
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
20
|
| Complexity |
297
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(SC=N1)CCOC2=CC=C(C=C2)C3=CC=NN3
|
| InChi Key |
QVEFQEQVSXFMCV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H15N3OS/c1-11-15(20-10-16-11)7-9-19-13-4-2-12(3-5-13)14-6-8-17-18-14/h2-6,8,10H,7,9H2,1H3,(H,17,18)
|
| Chemical Name |
4-methyl-5-[2-[4-(1H-pyrazol-5-yl)phenoxy]ethyl]-1,3-thiazole
|
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5043 mL | 17.5217 mL | 35.0435 mL | |
| 5 mM | 0.7009 mL | 3.5043 mL | 7.0087 mL | |
| 10 mM | 0.3504 mL | 1.7522 mL | 3.5043 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
