| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
p38alpha inhibitor 5 targets the ATP-binding pocket of p38alpha MAPK (MAPK14), a serine/threonine kinase that plays a key role in inflammatory responses and cancer. As a PROTAC-type ligand, it is designed to bind to p38alpha with high affinity, serving as the target protein ligand in a PROTAC molecule. It does not directly inhibit p38alpha (or it may have weak inhibition), but when conjugated to an E3 ligase ligand (e.g., VHL or CRBN) via a linker, the resulting PROTAC (NR-11c) induces ubiquitination and proteasomal degradation of p38alpha. This warhead is the ATP-competitive inhibitor PH-797804.
|
|---|---|
| ln Vitro |
In vitro, p38alpha inhibitor 5 is a PROTAC-type target protein ligand targeting p38alpha and can be used to synthesize NR-11c. As a single agent, it may have weak p38alpha inhibitory activity (as an ATP-competitive inhibitor). However, its primary use is as a building block for PROTAC synthesis. The binding affinity to p38alpha is not specified, but the parent compound PH-797804 has a p38alpha IC50 of <1 nM. p38alpha inhibitor 5 is not used as a therapeutic agent; it is a chemical tool.
|
| ln Vivo |
Not applicable. p38alpha inhibitor 5 is a synthetic intermediate for the PROTAC NR-11c. It is not administered in vivo as a single agent. In vivo, the corresponding PROTAC NR-11c degrades p38alpha in the liver of mice after intraperitoneal administration. p38alpha inhibitor 5 itself is not a drug candidate. No therapeutic in vivo activity is reported.
|
| Enzyme Assay |
The binding of p38alpha inhibitor 5 to p38alpha can be assessed by surface plasmon resonance (SPR). Recombinant p38alpha protein is immobilized on a sensor chip. Varying concentrations of p38alpha inhibitor 5 (0.1-1000 nM) are injected. The Kd is calculated. For quality control, the purity (>98%) is assessed by HPLC. The structure is confirmed by ¹H NMR, ¹3C NMR, and mass spectrometry (ESI-MS, expected [M+H]+ m/z 530). The compound is a brominated, fluorinated small molecule.
|
| Cell Assay |
Not applicable. p38alpha inhibitor 5 is a synthetic intermediate, not a drug. It is not used in standard cell-based assays for drug discovery. For toxicity screening, HepG2 or HEK293 cells are seeded in 96-well plates (1×10⁴ cells/well) and treated with the compound (1-1000 uM) for 24-72 h. Cell viability is measured by MTT assay. The CC₅0 is expected to be >100 uM, indicating moderate to low cytotoxicity. The compound is a building block for PROTAC synthesis.
|
| Animal Protocol |
No in vivo animal protocol for p38alpha inhibitor 5 exists, as it is not a drug candidate. For acute toxicity testing, female Sprague-Dawley rats (n=3-5 per dose) are administered a single oral dose of the compound in 0.5% methylcellulose at 100, 200, 500, 1000 mg/kg and observed for 14 days for mortality and clinical signs. The LD₅0 is expected to be >500 mg/kg (moderate acute toxicity). This protocol is not typically performed for this intermediate.
|
| ADME/Pharmacokinetics |
No PK data for p38alpha inhibitor 5 is available. As a small, lipophilic molecule (MW 529.37, LogP ~3-4), it would be absorbed if ingested. It is not intended for systemic administration. The compound is a synthetic intermediate, not a drug. For research use, it is stored at -20degC in a tightly sealed container, protected from light and moisture.
|
| Toxicity/Toxicokinetics |
For p38alpha inhibitor 5, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: at -20degC, sealed, protect from light.
|
| References | |
| Additional Infomation |
p38alpha inhibitor 5 (Compound 1, CAS# 2550397-96-9) is a research-grade PROTAC-type target protein ligand for p38alpha. It is not an FDA-approved drug. It is used as a building block for the synthesis of the p38alpha PROTAC degrader NR-11c. For research use only, not for diagnostic or therapeutic applications. Purity: ≥98%. Storage: -20degC, sealed, protect from light.
|
| Molecular Formula |
C26H23BRF2N2O3
|
|---|---|
| Molecular Weight |
529.37
|
| CAS # |
2550397-96-9
|
| Appearance |
Light yellow to yellow solid powder
|
| 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 (~188.90 mM; with ultrasonication)
|
|---|---|
| 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 | 1.8890 mL | 9.4452 mL | 18.8904 mL | |
| 5 mM | 0.3778 mL | 1.8890 mL | 3.7781 mL | |
| 10 mM | 0.1889 mL | 0.9445 mL | 1.8890 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
