| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
| Targets |
NIH-12848 targets phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ), an enzyme that phosphorylates phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂). PI5P4Kγ is involved in cellular signaling, membrane trafficking, and cell growth. The compound shows selectivity for the γ isoform over the α and β isoforms. This selectivity makes it a valuable tool for studying PI5P4Kγ-specific functions.
|
|---|---|
| ln Vitro |
At doses up to 100 μM, NIH-12848 does not inhibit the α and β PI5P4K isoforms, but it does inhibit PI5P4Kγ with an IC50 of roughly 1 μM. When mpkCCD cells reach confluence, NIH-12848 inhibits the translocation of Na+/K+-ATPase to the plasma membrane, hence reversibly preventing "dome" formation on the culture dish. One could replicate the effects of NIH-12848 by specifically knocking down PI5P4Kγ using RNA interference, but not PI5P4Ks α or β. NIH-12848 could be a useful instrument for investigating PI5P4Ks' cellular physiology [1].
In vitro, NIH-12848 inhibits PI5P4Kγ with an IC₅₀ of approximately 1 μM. It shows no inhibition of PI5P4Kα and PI5P4Kβ at concentrations up to 100 μM. The compound's selectivity profile has been characterized in biochemical assays. It is a specific inhibitor of the γ isoform. Detailed in vitro data are available in the primary literature. |
| ln Vivo |
In vivo data for NIH-12848 are limited in publicly available sources. The compound has been used in studies to characterize the absorption, pharmacokinetics, distribution, and metabolism of PI5P4K inhibitors. Further studies are needed to fully characterize its in vivo efficacy and pharmacokinetic profile. The compound is a research tool for lipid kinase studies.
|
| Enzyme Assay |
In vitro kinase assays for NIH-12848 typically use recombinant PI5P4Kγ enzyme and a lipid substrate (e.g., PI5P). The compound is dissolved in DMSO and diluted in assay buffer (50 mM Tris-HCl, pH 7.5, 10 mM MgCl₂, 1 mM DTT). Reactions are initiated by adding ATP (at Km concentration) and incubated at 30°C for 30-60 minutes. Product formation (PI(4,5)P₂) is detected by ELISA, radioactive methods, or mass spectrometry. IC₅₀ values are calculated from dose-response curves. Selectivity is assessed against PI5P4Kα and PI5P4Kβ isoforms.
|
| Cell Assay |
For cell-based assays, relevant cell lines (e.g., HeLa, HEK-293) are cultured in DMEM with 10% FBS. Cells are seeded in 6-well or 96-well plates and treated with NIH-12848 at various concentrations (0.1-100 μM) for 1-24 hours. PI5P4K activity may be assessed by measuring PI(4,5)P₂ levels or downstream signaling. Cell viability is assessed by MTT or CellTiter-Glo. All treatments include vehicle controls and are performed in triplicate.
|
| Animal Protocol |
In vivo, NIH-12848 may be administered to rodents via IP or oral routes. Formulation may involve DMSO or suitable vehicles. Pharmacodynamic studies assess PI5P4Kγ inhibition in tissues. Pharmacokinetic studies measure plasma and tissue concentrations. Bioanalytical methods have been developed for PK and toxicokinetic studies. All procedures follow institutional animal care guidelines.
|
| ADME/Pharmacokinetics |
NIH-12848 is a specific PI5P4Kγ inhibitor with an IC₅₀ of approximately 1 μM. It shows selectivity over PI5P4Kα and PI5P4Kβ (>100 μM). Bioanalytical methods have been developed for PK studies. Detailed pharmacokinetic parameters are available from preclinical studies. The compound is designed for research applications in lipid signaling.
|
| Toxicity/Toxicokinetics |
Toxicology data for NIH-12848 are limited in publicly available sources. As a kinase inhibitor, potential off-target effects should be considered. The compound is for research use only and not intended for human therapeutic applications. Standard safety pharmacology and toxicology studies would be required for therapeutic development. The compound should be handled with standard laboratory safety precautions.
|
| References | |
| Additional Infomation |
NIH-12848 is a research-grade PI5P4Kγ inhibitor for studying lipid kinase signaling. Its primary applications include cell biology, signal transduction, and drug discovery research. The compound is not approved for clinical use. It is commercially available from chemical suppliers for research purposes only. Its mechanism involves selective inhibition of PI5P4Kγ.
|
| Molecular Formula |
C20H14F3N3S
|
|---|---|
| Molecular Weight |
385.405473232269
|
| Exact Mass |
385.086
|
| Elemental Analysis |
C, 62.33; H, 3.66; F, 14.79; N, 10.90; S, 8.32
|
| CAS # |
959551-10-1
|
| Related CAS # |
959551-10-1
|
| PubChem CID |
3235425
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.6
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
27
|
| Complexity |
490
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
QBDAEJRHUCSSPR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H14F3N3S/c21-20(22,23)16-9-3-1-7-14(16)19-25-17-10-4-2-8-15(17)18(26-19)24-12-13-6-5-11-27-13/h1-11H,12H2,(H,24,25,26)
|
| Chemical Name |
N-(thiophen-2-ylmethyl)-2-(2-(trifluoromethyl)phenyl)quinazolin-4-amine
|
| Synonyms |
NIH-12848 NIH 12848 NIH12848, NCGC00012848-02.
|
| 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 : ≥ 100 mg/mL (~259.46 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.49 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 (6.49 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 | 2.5946 mL | 12.9732 mL | 25.9464 mL | |
| 5 mM | 0.5189 mL | 2.5946 mL | 5.1893 mL | |
| 10 mM | 0.2595 mL | 1.2973 mL | 2.5946 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
