| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
AG-1478 (also known as Tyrphostin AG1478; AG-1478; NSC-693255) is a novel, potent and selective EGFR (epidermal growth factor receptor) inhibitor with potential antitumor and antidiabetic activity. In cell-free experiments, it inhibits EGFR with an IC50 of 3 nM. Additionally, AG-1478 reversibly blocks Kv1.5 potassium channels in the rat brain, with an IC50 of 9.8 µM, without affecting PTK activity. AG-1478 exhibits strong anti-proliferative properties in vitro against cell cultures of leiomyoma and myometrium, with IC50 values of 5.6 and 5.7 µM, correspondingly. According to earlier research, EGFR antagonists may be useful in the treatment of a number of illnesses, including diabetes-related cardiomyopathy, angiotensin II-induced cardiac hypertrophy, and cancer. AG-1478 may therefore be utilized as a therapeutic for these conditions.
| Targets |
EGFR (IC50 = 3 nM); HCV; EMCV
|
|---|---|
| ln Vitro |
AG-1478 (AG1478) is irreversible for controlling the growth of human lung (A549) and prostate (DU145) cancer cell lines that were grown in DMEM/F12 medium that had been chemically defined. Although AG-1478 is not able to totally stop the growth of A549 cells, it appears to be more effective at lower concentrations[1]. The angiotensin II-mediated synthesis of TGF-β and fibronectin by cardiac fibroblasts is significantly reduced when EGFR is inhibited by the specific tyrosine kinase inhibitor AG-1478 (AG1478). AG-1478, a small-molecule inhibitor with an IC50 of 4 nM, pharmacologically inhibits EGFR[2]. Flow cytometry shows that both Polyfect (PF) and Superfect (SF) treatments increase apoptosis in HEK 293 cells to a comparable degree. For both PF and SF, the antioxidant tempol significantly decreased dendrimer-mediated apoptosis. AG-1478 (AG1478) was used as a positive control and significantly induced apoptosis in HEK 293 cells at a 10-fold higher dose (100 μM) than used in signaling studies[3].
|
| ln Vivo |
The administration of AG-1478 (AG1478) in both of the obese mouse models significantly reduces apoptosis, fibrosis, inflammation, and cardiac dysfunction. The ApoE-HFD protocol involves feeding ApoE-/- mice HFD for the first 8 weeks, followed by oral gavage administration of AG-1478 (10 mg/kg/day) or 542 (10 mg/kg/day) for an additional 8 weeks. Low density lipoprotein (LDL) and total triglyceride (TG) levels in plasma are unaffected by AG-1478 or 542 treatment, which inhibits HFD-induced cardiac EGFR phosphorylation in vivo[2]. A well-known EGFR phosphorylation inhibitor called AG-1478 (AG478) can prevent the strong and consistent increase in EGFR phosphorylation that occurs when EGF (10 nM) is administered.
|
| Enzyme Assay |
AG-1478 has an IC50 of >100 μM and is highly selective against ErbB2 and PDGFR. In U87MG cells, AG-1478 preferentially inhibits truncated EGFR expression (IC50 = 8.7 μM) over endogenous wt EGFR expression (IC50 = 34.6 μM and 48.4 μM, respectively), and inhibits DNA synthesis (IC50 = 4.6 μM, 19.67 μM, and 35.2 μM, respectively). Additionally, compared to endogenous or overexpressed exogenous wt EGFR, AG-1478 preferentially inhibits the tyrosine kinase activity and autophosphorylation of the ΔEGFR. In the VSMC, AG-1478 (0.25 μM) eliminates the MAPK activation caused by Ang II, a Ca2+ ionophore, and EGF, but not by a phorbol ester or platelet-derived growth factor-BB. With IC50 values of 0.07 μM and 0.2 μM, respectively, AG-1478 suppresses the EGF-induced mitogenesis of the BaF/ERX and LIM1215 cells. The ATP-binding cassette (ABC) transporters ABCB1 and ABCG2 can be inhibited by AG1478, with a greater effect on ABCG2.
|
| Cell Assay |
A549 (CCL-185) and DU145 (HTB-81) cells are seeded at a density of 4×103 cells/well in either DMEM (A549 cells) or MEM (DU145 cells) on 96-well plates. After a 24-hour incubation period, serum-free DMEM/F12 (1:1) enhanced with albumin (0.5 mg/mL), sodium selenite (2 ng/mL), and transferrin (5 mg/mL) is substituted for the culture medium (DMEM/F12+). Day 0 of the incubation period is followed by a replacement of the medium with serum-free DMEM/F12+ containing tyrosine kinase inhibitors (AG494, AG-1478) at concentrations of 1–20 μM and 0.1–8 μM, respectively. For the next twenty-four hours, the incubation is maintained at 37°C in a humidified environment. Tyrphostins' impact on target cell proliferation is assessed using the MTT assay and the modified crystal violet staining method (CV). Tecan multiscan plate recorder is used to measure absorbance[1].
|
| Animal Protocol |
Mice: Four weight-matched groups of 28 C57BL/6 or ApoE-/- mice are created at random. As a normal control group (ApoE-LF), seven mice are fed a standard animal low-fat diet consisting of 10 kcal% fat, 20 kcal% protein, and 70 kcal% carbohydrates. The remaining twenty-one mice are fed a high-fat diet consisting of 60 kcal% fat, 20 kcal% protein, and 20 kcal% carbohydrates for a period of 16 weeks. AG-1478 or 542 are given orally via gavage starting in the 9th week, with a daily dose of 10 mg/kg for the following eight weeks. Only the vehicle (1% CMC-Na solution) is gavaged on mice in the Control and HFD groups. To ascertain the pathologic cardiac hypertrophy, doppler analysis is carried out the day prior to the sacrifice of ApoE-/- mice.
Rats: In this study, five groups of male Wistar rats, weighing approximately 300g, were utilized. Animals in Group 1 that are not diabetic (Control, C) The second group received a single intraperitoneal (i.p.) injection of C+PF (10 mg/kg). Groups 4 and 3 are C+AG-1478 (1 mg/kg i.p.) and C+SF (10 mg/kg i.p.). Group 5: Rats given a single intraperitoneal injection of streptozotocin (55 mg/kg body weight) for four weeks to induce diabetes (D); Group 6: D+PF (10 mg/kg i.p.) Groups 7 and 8 consist of D+SF (10 mg/kg i.p.) and D+AG-1478 (1 mg/kg i.p.). The treatments for dendrimer and AG-1478 are given as a single dose 24 hours before sacrifice. Before the animals are killed, measurements of the rats' basal glucose levels and body weight are taken both before and after the treatments. Blood glucose levels are measured using an automated blood glucose analyzer, and as in earlier research, rats with blood glucose levels greater than 250 mg/dL (roughly 14 mM) are classified as diabetic.
|
| References |
|
| Molecular Formula |
C16H14CLN3O2
|
|---|---|
| Molecular Weight |
315.75
|
| Exact Mass |
315.08
|
| Elemental Analysis |
C, 60.86; H, 4.47; Cl, 11.23; N, 13.31; O, 10.13
|
| CAS # |
153436-53-4
|
| Related CAS # |
AG-1478 hydrochloride;170449-18-0
|
| Appearance |
Solid powder
|
| SMILES |
COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=CC=C3)Cl)OC
|
| InChi Key |
GFNNBHLJANVSQV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H14ClN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20)
|
| Chemical Name |
N-(3-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine
|
| Synonyms |
Tyrphostin AG-1478; AG1478; Tyrphostin AG 1478; NSC 693255; NSC-693255; NSC693255
|
| 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) |
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1671 mL | 15.8353 mL | 31.6706 mL | |
| 5 mM | 0.6334 mL | 3.1671 mL | 6.3341 mL | |
| 10 mM | 0.3167 mL | 1.5835 mL | 3.1671 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.
Small molecule EGFR inhibitors attenuate HFD-induced EGFR phosphorylation and myocardial fibrosis in ApoE−/−mouse hearts.Sci Rep.2016 Apr 18;6:24580. |
542 or AG1478 suppress HFD-induced inflammation in ApoE−/−mouse hearts.Sci Rep.2016 Apr 18;6:24580. |
EGFR inhibitors reverse HFD-induced hypertrophic remodeling, fibrosis and apoptosis in C57BL/6 mouse heart.Sci Rep.2016 Apr 18;6:24580. |
EGFR inhibitors attenuate PA-induced inflammation in H9C2 Cells.Sci Rep.2016 Apr 18;6:24580. |
EGFR inhibitors reverse PA-induced hypertrophy, fibrosis and apoptosis in H9C2 cells.Sci Rep.2016 Apr 18;6:24580. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
