BMS-536924

Catalog No.S1012 Synonyms: CS-0117

For research use only.

BMS-536924 (CS-0117) is an ATP-competitive IGF-1R/IR inhibitor with IC50 of 100 nM/73 nM, modest activity for Mek, Fak, and Lck with very little activity for Akt1, MAPK1/2.

BMS-536924 Chemical Structure

CAS No. 468740-43-4

Selleck's BMS-536924 has been cited by 19 publications

Purity & Quality Control

Choose Selective IGF-1R Inhibitors

Other IGF-1R Products

Biological Activity

Description BMS-536924 (CS-0117) is an ATP-competitive IGF-1R/IR inhibitor with IC50 of 100 nM/73 nM, modest activity for Mek, Fak, and Lck with very little activity for Akt1, MAPK1/2.
Targets
Insulin Receptor [1] IGF-1R [1]
()
FAK [1] MEK [1] LCK [1] Click to View More Targets
73 nM 100 nM 150 nM 182 nM 341 nM
In vitro

BMS-536924 also inhibits FAK and Lck with IC50 of 150 nM and 341 nM, respectively. BMS-536924 inhibits cellular proliferation and disrupts Akt and MAPK phosphorylation. [1] BMS-536924 inhibits IGF-I-stimulated IGF-1R signaling in MCF10A cells and blocks constitutive IGF-1R activity in CD8-IGF-1R-MCF10A. Preincubation of MCF10A cells with 1 μM BMS-536924 completely blocks the ability of IGF-I to stimulate IGF-1R phosphorylation. IGF-I stimulation results in increased phosphorylation of ERK1/2, GSK3β, and Akt. BMS-536924 inhibits this ligand-induced phosphorylation. Treatment of the CD8-IGF-1R-MCF10A cells with BMS-536924 results in a dose-dependent inhibition of phosphorylation with partial inhibition at 0.01 μM and 0.1 μM, but complete receptor inhibition at a concentration of 1 μM. Maximal inhibition of phosphorylated IGF-1R is observed as early as 10 minutes following incubation. BMS-536924 retains its ability to inhibit IGF-1R phosphorylation for up to 48 hours. Addition of BMS-536924 time-dependently inhibits Akt phosphorylation starting at 1 hour. By 48 hours, Akt activation is completely blocked. [2] Treatment with BMS-536924 shows antiproliferation activity in a panel of cancer cell lines including TC32, HT1080/S, SK-LMS-1, H513 and CTR cells. pIGF-1R/pIR is activated upon IGF-I/insulin stimulation and the activation is inhibited by BMS-536924 at similar potencies in Rh41 and Rh36 cell lines. The expression of programmed cell death 4 (PDCD4), cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 are up-regulated in Rh41 cells treated with BMS-536924. [3]

In vivo Oral administration of BMS-536924 at 100-300 mpk strongly inhibits IGR-1R Sal tumor model. Efficacy is also observed in the nonengineered Colo205 human colon carcinoma mode. Oral administration of 3 on a once a day schedule (100-300 mpk) or a twice a day schedule (50, 100 mpk) demonstrates antitumor activity in this tumor model. Oral glucose tolerance test (OGTT) shows 100 mpk (b.i.d.) causes a significant elevation in glucose levels after glucose challenge. The pharmacokinetic parameters of BMS-536924, administered orally in poly(ethylene glycol) 400 and water (80:20 v/v), are determined in mouse, rat, dog, and monkey. Good bioavailability is evident in all species. Significant nonlinear pharmacokinetics is observed in rodents at increasing p.o. dose. [1] BMS-536924 reduces the tumor xenografts volume of CD8-IGF-1R-MCF10A cells after two weeks' treatment (100mg/kg) to 76%. [2] Oral administration of 70 mg/kg BMS-536924 significantly inhibits tumor growth (TGBC-1TKB cells) inoculated in nude mice. BMS-536924 up regulates apoptosis in xenografts tumors. The treatment doesn't have adverse effects on the body weight of mice or the glucose levels at the time of death, suggesting tolerable toxicity. [4]

Protocol (from reference)

Kinase Assay:

[2]

  • IGF-I Pathway Activity:

    1 × 106 pBabe-MCF10A cells are seeded onto 60-mm dishes. After 24 hours, the medium is changed to serum-free medium and incubated overnight at 37 °C for 24 hours. Cells are then pre-incubated with or without 1 uM BMS-536924 for 1 hour in serum free medium followed by stimulation with IGF-I (50 ng/mL) for 10 minutes. Cell monolayers are washed twice with PBS and harvested for immunoblot analysi

Cell Research:

[3]

  • Cell lines: TC32, HT1080/S, SK-LMS-1, H513 and CTR cells
  • Concentrations: 10 nM - 5 μM
  • Incubation Time: 72 hours
  • Method:

    Cell proliferation is evaluated by [3H]thymidine incorporation after exposure to BMS-536924 for 72 hours. Cells are plated at an optimized density in 96-well plates, incubated overnight at 37 °C, and then exposed to a serial dilution of the drug. After a 72-hours incubation, cells are pulsed with 4 μCi/mL [3H]thymidine for 3 hours, trypsinized, harvested onto UniFilter-96 GF/B plates; scintillation is measured on a TopCount NXT. Results are expressed as an IC50. The mean IC50 and SD from multiple tests for each cell line are calculated.

Animal Research:

[4]

  • Animal Models: TGBC-1TKB cells are subcutaneously injected into nude mice.
  • Dosages: 70 mg/kg
  • Administration: Oral once daily for 2 weeks

Solubility (25°C)

In vitro

DMSO 96 mg/mL
(200.01 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 479.96
Formula

C25H26ClN5O3

CAS No. 468740-43-4
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC(=CC2=C1N=C(N2)C3=C(C=CNC3=O)NCC(C4=CC(=CC=C4)Cl)O)N5CCOCC5

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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

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

Frequently Asked Questions

Question 1:
What are the differences between S1012 ans S1034?

Answer:
The most remarkable difference between these two IGF-IR inhibitors is S1012 BMS-536924 is a ATP-competitive inhibitor. You will get more information differences between IR inhibitors in this reference: http://www.sciencedirect.com/science/article/pii/S1359644605035129.

Tags: buy BMS-536924 | BMS-536924 supplier | purchase BMS-536924 | BMS-536924 cost | BMS-536924 manufacturer | order BMS-536924 | BMS-536924 distributor