| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
R 59949 targets diacylglycerol kinase (DGK), an enzyme that phosphorylates diacylglycerol (DAG) to phosphatidic acid, thereby terminating DAG signaling. It acts as a pan-DGK inhibitor with an IC50 of 300 nM. By inhibiting DGK, it increases DAG levels, which activates protein kinase C (PKC). It inhibits inducible NO production through decreasing transplasmalemmal L-arginine uptake.
|
|---|---|
| ln Vitro |
Vasopressin- and collagen-induced release response and aggregation are markedly enhanced in the presence of R59949, which is linked to the production of arachidonic acid metabolites [1]. R59949 restricts the import of CCL2 in THP-1 monocytes. By decreasing the concentration of L-arginine solution across the plasma membrane in vascular smooth muscle cells, R59949 adsorbs the generation of inducible nitric oxide [4]. Half maximal concentration of the Ca2+ signal is 8.6 μM[2].
In vitro, R 59949 is a pan-diacylglycerol kinase (DGK) inhibitor with an IC50 of 300 nM. It strongly inhibits type I DGKα and γ and moderately inhibits type II DGKθ and κ. It activates PKC by increasing DAG levels. It inhibits inducible NO production in rat aortic smooth muscle cells (RASMCs). |
| ln Vivo |
In vivo, R 59949 is used as a research tool to study the role of DGK and PKC in various physiological and pathological processes. However, specific details of in vivo efficacy studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use.
|
| Enzyme Assay |
The in vitro enzyme assay for R 59949 measures its ability to inhibit diacylglycerol kinase (DGK) activity. These cell-free assays use purified DGK or membrane preparations and measure the phosphorylation of DAG. The compound's inhibitory potency (IC50) is determined by measuring the reduction in enzyme activity.
|
| Cell Assay |
In vitro cellular assays for R 59949 assess its effects on DAG levels and PKC activation. Cells are treated with R 59949, and DAG levels are measured. PKC activation is assessed by measuring the phosphorylation of PKC substrates. Its effects on NO production are also assessed.
|
| Animal Protocol |
In vivo animal studies for R 59949 are conducted to study the role of DGK in various disease models. However, specific details of these studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use.
|
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for R 59949 are not extensively detailed in the available literature. As a small molecule, its pharmacokinetic properties would be important for its in vivo efficacy. However, specific parameters such as half-life and bioavailability are not provided. It is intended for research use only.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for R 59949 are not extensively detailed in the available literature. As a DGK inhibitor, its toxicity profile is likely related to its mechanism of action. However, its use in research suggests a manageable safety profile. It is intended for research purposes only.
|
| References |
|
| Additional Infomation |
3-[2-[4-[bis(4-fluorophenyl)methylene]-1-piperidinyl]ethyl]-2-thiomethylene-1H-quinazolin-4-one is a diarylmethane.
R 59949 is a pan-diacylglycerol kinase (DGK) inhibitor with an IC50 of 300 nM. It inhibits type I DGKα and γ and type II DGKθ and κ. It activates PKC by increasing DAG levels. It is a research compound for studying DGK and PKC signaling. It is not approved for clinical use. |
| Molecular Formula |
C28H25F2N3OS
|
|---|---|
| Molecular Weight |
489.58
|
| Exact Mass |
489.169
|
| CAS # |
120166-69-0
|
| PubChem CID |
657356
|
| Appearance |
White to off-white solid powder
|
| Density |
1.36g/cm3
|
| Boiling Point |
637.1ºC at 760mmHg
|
| Flash Point |
339.1ºC
|
| Vapour Pressure |
3.94E-16mmHg at 25°C
|
| Index of Refraction |
1.688
|
| LogP |
5.873
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
770
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
ZCNBZFRECRPCKU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C28H25F2N3OS/c29-22-9-5-19(6-10-22)26(20-7-11-23(30)12-8-20)21-13-15-32(16-14-21)17-18-33-27(34)24-3-1-2-4-25(24)31-28(33)35/h1-12H,13-18H2,(H,31,35)
|
| Chemical Name |
3-(2-(4-(bis(4-fluorophenyl)methylene)piperidin-1-yl)ethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
|
| Synonyms |
R-59949 R59949 R 59949
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~100 mg/mL (~204.26 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.11 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 | 2.0426 mL | 10.2128 mL | 20.4257 mL | |
| 5 mM | 0.4085 mL | 2.0426 mL | 4.0851 mL | |
| 10 mM | 0.2043 mL | 1.0213 mL | 2.0426 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
