| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
Double-stranded RNA-dependent protein kinase (PKR), an apoptotic inducer that regulates pro-inflammatory cytokine production. C16 is a specific PKR inhibitor that binds to the ATP-binding site of PKR and blocks autophosphorylation. The compound has an IC50 of 186-210 nM for PKR inhibition. It is a brain-penetrant compound with anti-inflammatory effects.
|
|---|---|
| ln Vitro |
In primary neuronal cultures, PKR-IN-C16 (compound C16) releases the PKR-induced translation block [1]. In SH-SY5Y cells, PKR-IN-C16 (0.1 or 0.3 μM; 24 hours) prevents endoplasmic reticulum stress-induced neuronal cell death [1]. In addition to inhibiting PKR phosphorylation, PKR-IN-C16 (1-1000 nM; 4 hours) also stops amyloid beta-induced caspase-3 activation in SH-SY5Y cells [2].
C16 inhibits PKR autophosphorylation with an IC50 of 186-210 nM. It also inhibits caspase-3 and caspase-8, and prevents increases in pT(451)-PKR and pS(194)-FADD levels in SH-SY5Y nuclei. C16 protects human neuroblastoma cells against cell damage triggered by tunicamycin-mediated endoplasmic reticulum stress. The compound has anti-inflammatory effects and shows promising neuroprotective properties. |
| ln Vivo |
PKR-IN-C16 (compound C16) (60 or 600 μg/kg; i.p.; 3 times) prevents both the inflammatory response in the model and PKR-induced neuronal loss in rats. It also prevents quinolinic acid (QA)-induced acute excitotoxicity.
In vivo, C16 has been shown to effectively inhibit PKR function and has neuroprotective and nootropic effects in animal studies. The compound rescues acute brain lesions. It is a brain-penetrant PKR inhibitor with anti-inflammatory effects. Further in vivo studies are needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro enzyme assays for C16 involve measuring the inhibition of PKR autophosphorylation. PKR is incubated with ATP and various concentrations of C16. Autophosphorylation is assessed by Western blot using phospho-specific antibodies or by measuring kinase activity using appropriate substrates. IC50 values (186-210 nM) are determined from concentration-response curves.
|
| Cell Assay |
Western Blot Analysis[2]
Cell Types: Human SH-SY5Y Cell Tested Concentrations: 1, 10, 20, 200, 1000 nM Incubation Duration: 4 hrs (hours) Experimental Results: Significant levels of phosphorylated PKR in cells exposed to 20 μM beta-amyloid reduce. In vitro cellular assays for C16 involve treating cells (such as SH-SY5Y neuroblastoma cells) with the compound and measuring PKR phosphorylation, cell viability, and apoptosis. Cells are treated with various concentrations of C16, and PKR phosphorylation is measured by Western blot. C16 protects human neuroblastoma cells against cell damage triggered by tunicamycin-mediated endoplasmic reticulum stress. |
| Animal Protocol |
Animal/Disease Models: normotensive male Wistar rats, excitotoxic neuroinflammation model, unilateral striatal injection of quinolinic acid (QA) to induce inflammation [1]
Doses: 60 or 600 μg/kg Mode of Route of Administration: intraperitoneal (ip) injection; 24 hrs (hrs (hours)) before, 2 hrs (hrs (hours)) after QA injection and 24 hrs (hrs (hours)) after QA injection Experimental Results: diminished expression of PKR active catalytic domain, preventing contralateral IL-1β levels from increasing at 600 μg/kg (97% inhibition ). Neuronal loss induced by 600 μg/kg QA injection was diminished by 47%, and the number of positively cleaved caspase-3 neurons was diminished by 37%. In vivo animal studies for C16 typically involve administration to rodent models of neurological disorders or brain injury. The compound rescues acute brain lesions and has shown neuroprotective and nootropic effects. Efficacy is assessed by measuring neurological function, lesion size, and molecular markers of inflammation and apoptosis. Pharmacokinetic parameters are determined from serial blood sampling. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of C16 show that the compound is brain-penetrant. It has a molecular weight of 268.29 and a molecular formula of C13H8N4OS. The compound is slightly soluble in DMSO and should be stored at -20°C. Further pharmacokinetic studies are needed to support its development as a therapeutic agent.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity studies of C16 suggest a favorable safety profile. The compound has been shown to protect human neuroblastoma cells against cell damage triggered by endoplasmic reticulum stress. It has anti-inflammatory effects and shows promising neuroprotective properties. Comprehensive toxicological evaluation is needed to support clinical development.
|
| References |
|
| Additional Infomation |
Imidazolo-oxindole PKR inhibitor C16 is a pKR inhibitor.
C16 (PKR-IN-C16, GW-506033X) is a specific, brain-penetrant inhibitor of double-stranded RNA-dependent protein kinase (PKR) with an IC50 of 186-210 nM. It binds to the ATP-binding site of PKR and blocks autophosphorylation. C16 inhibits caspase-3 and caspase-8, and protects human neuroblastoma cells against ER stress-induced damage. The compound has anti-inflammatory effects and shows neuroprotective and nootropic properties in animal studies, rescuing acute brain lesions. |
| Molecular Formula |
C13H8N4OS
|
|---|---|
| Molecular Weight |
268.294
|
| Exact Mass |
268.041
|
| CAS # |
608512-97-6
|
| PubChem CID |
6490494
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.6±0.1 g/cm3
|
| Boiling Point |
674.6±55.0 °C at 760 mmHg
|
| Flash Point |
361.8±31.5 °C
|
| Vapour Pressure |
0.0±2.1 mmHg at 25°C
|
| Index of Refraction |
1.851
|
| LogP |
0.8
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
19
|
| Complexity |
427
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC2=C(C\3=C1NC(=O)/C3=C\C4=CN=CN4)SC=N2
|
| InChi Key |
VFBGXTUGODTSPK-BAQGIRSFSA-N
|
| InChi Code |
InChI=1S/C13H8N4OS/c18-13-8(3-7-4-14-5-15-7)11-9(17-13)1-2-10-12(11)19-6-16-10/h1-6H,(H,14,15)(H,17,18)/b8-3-
|
| Chemical Name |
6,8-dihydro-8-(1H-imidazol-5-ylmethylene)-7H-pyrrolo[2,3-g]benzothiazol-7-one
|
| Synonyms |
GW 506033XC16 GW-506033X PKR InhibitorGW506033X
|
| 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 : ~10 mg/mL (~37.27 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7273 mL | 18.6366 mL | 37.2731 mL | |
| 5 mM | 0.7455 mL | 3.7273 mL | 7.4546 mL | |
| 10 mM | 0.3727 mL | 1.8637 mL | 3.7273 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
