| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
AG-18 (also known as RG-50810, RG-50858, TX 825, Tyrphostin A23 and Tyrphostin AG-18) is a novel and potent EGFR inhibitor with an IC50 and Ki of 35 and 11 μM, respectively. The AP-2 adaptor complex's medium chain subunit interacts with tyrosine motifs in a way that AG-18 disrupts, preventing the transferrin receptor from internalizing.
| Targets |
EGFR (IC50 = 35 μM); EGFR (Ki = 11 μM)
|
||
|---|---|---|---|
| ln Vitro |
AG 18 inhibits EGFR and IR with Ki of 11 μM and 12 mM. In A431 cells, AG 18 inhibits the autophosphorylation of EGFR induced by EGF at an IC50 of 15 μM.[1] GH3 cell proliferation induced by EGF is inhibited by AG 18 (10 μM). Significant inhibition of cell proliferation induced by 10 nM and 1 μM ghrelin is observed with AG 18 (10 μM). In GH3 cells, AG 18 (10 μM) inhibits the rise in ERK 1/2 phosphorylation induced by ghrelin. In primary astrocyte cultures,[2] AG 18 inhibits the volume-sensitive release of [3H]taurine in a dose-dependent manner. AG 18 causes primary astrocytic cultures to release D-[3H]aspartate in a volume-dependent manner in response to swelling.[3] In A549 epithelial cells, TPA-induced stimulation of ICAM-1 expression is inhibited in a dose-dependent manner by AG 18 (300 μM). In A549 epithelial cells, AG 18 (300 μM) also suppresses TPA-stimulated NF-kappaB DNA-protein binding and ICAM-1 promoter activity. In A549 epithelial cells, AG 18 (300 μM) dose-dependently suppresses TNF-alpha-induced NF-kappaB DNA-protein binding and ICAM-1 promoter activity. In A549 epithelial cells, TNF-alpha and TPA both increase IKK activity. AG 18 (100 μM) counteracts these effects.[4] In the carotid artery, AG 18 (10 μM) lowers the maximal contraction to 5-HT and diminishes the potency of 5-HT four times. AG 18 (10 μM) causes the maximum significantly inhibited contraction and shifts contraction induced by KCl twofold.[5]
|
||
| ln Vivo |
|
||
| Enzyme Assay |
EGF (800 nM) is added to WGA-purified A431 cell EGF receptor (0.5 μg/assay) and allowed to activate for 20 minutes at 4 °C. Mg(Ac)2 (60 mM), Tris-Mes buffer, pH 7.6 (50 mM), and [32P]ATP (20 pM, 5 μCi/assay) are added to start the reaction. At 4 °C or 15 °C, the reaction is carried out, and it is finished by adding sodium dodecyl sulfate (SDS) sample buffer (10% glycerol, pH 6.8, 50 mM Tris, 5% β-mercaptoethanol, and 3% SDS). The samples were run on an 8% SDS polyacrylamide gel (SDS-PAGE), which was made from 30% acrylamide and 0.8% bis-(acrylamide). The additives included pH 8.8, 0.1% SDS, 0.46% ammonium persulfate, 0.375 M Tris, and 0.05% TEMED. Agfa Curix RP2 X-ray film is used to perform autoradiography after the gel has dried. The Cerenkov mode is used to cut and count the pertinent radioactive bands. For an additional ten minutes, the fast phase of autophosphorylation persisted. The first site on the receptor is most likely phosphorylated, as evidenced by the 1/3 of the total autophosphorylation signal that is completed in the first 10 seconds at 15 °C. Therefore, the 10-s interval is selected to be used in the next autophosphorylation experiments.
|
||
| Cell Assay |
In a medium containing 2% charcoal-stripped FCS, different concentrations of ghrelin, desoctanoylated ghrelin, PMA, or EGF, GH3 cells are plated at a density of 5 × 104 cells/well for 72 hours.After that, 2 μCi/well [3H]thymidine is added for an additional 6 hours. For ghrelin stimulation, a time-course of 24, 48, and 72 hours is conducted; of these, 72 hours is chosen for additional research. Additionally, research is done to find out how rat ghrelin or desoctanoyl ghrelin stimulates cell proliferation. It also looks into how U0126, GF109203X, AG 18, wortmannin, and H-89 affect ghrelin-induced MAPK stimulation. Thirty minutes before each treatment, AG 18 at a concentration of 10 μM is added. The Microbeta 1450 bcounter is used to harvest the cells prior to counting them in the presence of scintillation fluid. At least three repetitions are made of each experiment.
|
||
| Animal Protocol |
|
||
| References |
| Molecular Formula |
C10H6N2O2
|
|
|---|---|---|
| Molecular Weight |
186.17
|
|
| Exact Mass |
186.04
|
|
| Elemental Analysis |
C, 64.52; H, 3.25; N, 15.05; O, 17.19
|
|
| CAS # |
118409-57-7
|
|
| Related CAS # |
|
|
| Appearance |
Light yellow solid powder
|
|
| SMILES |
C1=CC(=C(C=C1C=C(C#N)C#N)O)O
|
|
| InChi Key |
VTJXFTPMFYAJJU-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C10H6N2O2/c11-5-8(6-12)3-7-1-2-9(13)10(14)4-7/h1-4,13-14H
|
|
| Chemical Name |
2-[(3,4-dihydroxyphenyl)methylidene]propanedinitrile
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (13.43 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 (13.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 5.3714 mL | 26.8572 mL | 53.7143 mL | |
| 5 mM | 1.0743 mL | 5.3714 mL | 10.7429 mL | |
| 10 mM | 0.5371 mL | 2.6857 mL | 5.3714 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
COA