Home Protein Tyrosine Kinase IGF-1R inhibitor AG-1024

research use only

AG-1024 IGF-1R inhibitor

Cat.No.S1234

AG-1024 (Tyrphostin, AGS 200) inhibits IGF-1R autophosphorylation with IC50 of 7 μM, is less potent to IR with IC50 of 57 μM and specifically distinguishes between InsR and IGF-1R (as compared to other tyrphostins).
AG-1024 IGF-1R inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 305.17

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S123401 DMSO]61 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.99%
99.99

Chemical Information, Storage & Stability

Molecular Weight 305.17 Formula

C14H13BrN2O

 Storage (From the date of receipt)
CAS No. 65678-07-1 Download SDF Storage of Stock Solutions

Synonyms Tyrphostin, AGS 200 Smiles CC(C)(C)C1=C(C(=CC(=C1)C=C(C#N)C#N)Br)O

Solubility

In vitro
Batch:

DMSO : 61 mg/mL (199.88 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC50/Ki
IGF-1R [1]
(NIH-3T3 fibroblasts )
7 μM
Insulin Receptor [1]
(NIH-3T3 fibroblasts )
57 μM
In vitro
AG-1024 blocks the IGF-1 receptor and IR autophosphorylation with IC50 of 7 μM and 57 μM, respectively. This compound also inhibits the receptor tyrosine kinase activity towards exogenous substrates (TKA) with IC50 values of 18 μM and 80 μM, respectively. [1] This chemical (10 μM) inhibits cell proliferation in a time-dependent manner, and induces apoptosis in MCF-7 cells at 48 hours by 20.1% and >40% when combined with irradiation (10 Gy), more potently than that of irradiation (10 Gy) alone by 11.8%, which is associated with a down-regulation of phospho-Akt1 and bcl-2, and up-regulation of Bax, p53 and p21. [2] It significantly inhibits melanoma cell proliferation with an IC50 of <50 nM in the absence of serum, by blocking MAPK/ERK2 signaling, subsequently rapidly inducing pRb dephosphorylation and activation, and eventually the formation of growth suppressive pRb-E2F complexes. [3] Treatment with this compound down-regulates the expression of Bcr-Abl and P-Akt, and up-regulates DNA-PKcs expression in UT7-9 and Ba/F3-p210 cells, leading to decreased clonogenic survival and proliferation. It also significantly inhibits the proliferation of cells resistant to the BCR-ABL inhibitor STI571, which correlates with a dose-dependent decrease in Bcr-Abl protein expression. [4]
Kinase Assay
Inhibition of IGF-1- and insulin-stimulated cellular proliferation
NIH-3T3 cells overexpressing IGF-1 or insulin receptors are plated on 96-well plates (2,000-5,000 cells/well) and maintained overnight in complete medium. Cells are then changed to DMEM containing 1% FBS in the presence of 10 nM IGF-1 or insulin and various concentrations of AG-1024 for 120 hours. Medium is replaced every 48 hours. At the indicated periods of time, the medium is aspirated from the wells and 100 μL MTT is added to each well. The cells are then incubated for 4 hours at 37 °C and lysed by addition of 100 μL isoamylic alcohol and shaking for 20 minutes. The plate is then read in the ELISA reader at 570 and 690 nm. The IC50 value is calculated at the 120-hour time point.
In vivo
Administration of AG-1024 at a dose of 30 μg for 10 days significantly inhibits the tumor growth of Ba/F3-p210 xenograft in mice. [4]
References

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

Signaling Pathway Map