Home Tools
Log in
Cart

BMS-599626

Catalog No. T2610   CAS 714971-09-2
Synonyms: AC480

BMS-599626 (AC480) has been used in trials studying the treatment of Cancer, Metastases, and HER2 or EGFR Expressing Advanced Solid Malignancies.

All TargetMol products are for research or drug registration purposes only and cannot be used for human consumption. We do not provide products or services to individuals. Please comply with the intended use and do not use TargetMol products for any other purpose in violation of laws and regulations.
BMS-599626 Chemical Structure
BMS-599626, CAS 714971-09-2
Pack Size Availability Price/USD Quantity
10 mg 35 days $ 558.00
25 mg 35 days $ 1,270.00
Bulk Inquiry
Get quote
Select Batch  
Contact us for more batch information
Biological Description
Chemical Properties
Storage & Solubility Information
Description BMS-599626 (AC480) has been used in trials studying the treatment of Cancer, Metastases, and HER2 or EGFR Expressing Advanced Solid Malignancies.
Targets&IC50 HER1:20 nM, HER2:30 nM, HER4:190 nM
In vitro In vivo administration of BMS-599626, ranging from 60 mg/kg to 240 mg/kg, resulted in a dose-dependent inhibition of Sal2 tumor growth, demonstrating effective antitumor activity in its KPL-4 human breast cancer xenografts. The maximum tolerated dose was identified as 180 mg/kg. Similarly, this compound exhibited comparable antitumor activities in other HER2-amplified xenograft models as well as in various HER1-overexpressing xenograft models.
In vivo MS-599626 effectively inhibits the proliferation of tumor cells expressing high levels of HER1 and/or HER2, including Sal2, BT474, N87, KPL-4, HCC202, HCC1954, HCC1419, AU565, ZR-75-30, MDA-MB-175, GEO, and PC9 cells, with IC50 values of 0.24 μM, 0.31 μM, 0.45 μM, 0.38 μM, 0.94 μM, 0.34 μM, 0.75 μM, 0.63 μM, 0.51 μM, 0.84 μM, 0.90 μM, and 0.34 μM, respectively. BMS-599626 selectively inhibits the enzymatic activity of recombinant HER1 and HER2 kinases, with IC50 values of 20 nM and 30 nM, respectively. It significantly enhances the radiosensitivity of HN-5 cells expressing EGFR and Her2 by promoting cell cycle redistribution and inhibiting DNA repair. Furthermore, BMS-599626 also inhibits HER4, albeit with lower potency, showing an IC50 of 190 nM. However, it does not significantly inhibit the proliferation of the ovarian tumor cell line A2780 and the fibroblast cell line MRC5, which do not express HER1 or HER2.
Kinase Assay Protein kinase assays: The entire cytoplasmic sequences of HER1, HER2, and HER4 are expressed as recombinant proteins in Sf9 insect cells. HER1 and HER4 are expressed as fusion proteins with glutathione-S-transferase and are purified by affinity chromatography on glutathione-S-Sepharose. HER2 is subcloned into the pBlueBac4 vector and expressed as an untagged protein using an internal methionine codon (M687) for translation initiation. The truncated HER2 protein is isolated by chromatography on a column of DEAE-Sepharose equilibrated in a buffer that contains 0.1 M NaCl, and the recombinant protein is eluted with a buffer containing 0.3 M NaCl. For the HER kinase assays, reaction volumes are 50 μL and contains 10 ng of glutathione-S-transferase fusion protein or 150 ng of partially purified HER2. The mixtures also contains 1.5 μM poly(Glu/Tyr) (4:1), 1 μM ATP, 0.15 μCi [γ-33P]ATP, 50 mM Tris-HCl (pH 7.7), 2 mM DTT, 0.1 mg/mL bovine serum albumin, and 10 mM MnCl2. Reactions are allowed to proceed at 27°C for 1 hour and are terminated by the addition of 10 μL of a stop buffer (2.5 mg/mL bovine serum albumin and 0.3 M EDTA), followed by a 108-μL mixture of 3.5 mM ATP and 5% trichloroacetic acid. Acid-insoluble proteins are recovered on GF/C Unifilter plates with a Filtermate harvester. Incorporation of radioactive phosphate into the poly(Glu/Tyr) substrate is determined by liquid scintillation counting. Percent inhibition of kinase activity is determined by nonlinear regression analyses and data are reported as the inhibitory concentration required to achieve 50% inhibition relative to control reactions (IC50). Data are the averages of triplicate determinations. All other tyrosine kinases are also assayed using poly(Glu/Tyr) as a substrate. Kinetics of HER1 and HER2 inhibition are determined in reaction mixtures that contains varying concentrations of ATP and BMS-599626.
Cell Research All cell lines are maintained in RPMI 1640 supplemented with 10% fetal bovine serum, 100 units/mL penicillin, and 100 μg/mL streptomycin. Cells are plated at 1,000 per well in 96-well plates and are cultured for 24 hours before BMS-599626 is added. BMS-599626 is diluted in culture medium such that the final concentrations of DMSO are ≤ 1%. Following the addition of BMS-599626, the cells are cultured for an additional 72 hours before cell viability is determined by measuring the conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye with the CellTiter96 kit. For some cell lines, there is a lack of a correlation between 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye metabolism and cell number, and a thymidine uptake assay is used to measure proliferation of these cell lines. Cells are plated in 96-well plates and treated with compounds as above. At the end of the 72-hour incubation, cells are pulsed with [3H]thymidine (0.4 μCi/well) for 3 hours before they are harvested. Cells are digested with 2.5% trypsin for 10 minutes at 37 °C and are harvested by filtration using a Packard Filtermate Harvester and GF/C Unifilter plates. Incorporation of radioactive thymidine into nucleic acids is determined by liquid scintillation counting.(Only for Reference)
Synonyms AC480
Molecular Weight 530.55
Formula C27H27FN8O3
CAS No. 714971-09-2

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

H2O: <1 mg/mL

DMSO: 104 mg/mL (196 mM)

Ethanol: 16 mg/mL (30.2 mM)

TargetMolReferences and Literature

1. Wong TW, et al. Clin Cancer Res, 2006, 12(20 Pt 1), 6186-6193. 2. Torres MA, et al. Invest New Drugs, 2011, 29(4), 554-561. 3. Haluska P, et al. Mol Cancer Ther, 2008, 7(9), 2589-2598.

Related compound libraries

This product is contained In the following compound libraries:
Anti-Ovarian Cancer Compound Library

Related Products

Related compounds with same targets
lavendustin A Cloperastine fendizoate RG13022 WHI-P180 BGB-102 Mubritinib NRC-2694 Rociletinib

TargetMolDose Conversion

You can also refer to dose conversion for different animals. More

TargetMol In vivo Formulation Calculator (Clear solution)

Step One: Enter information below
Dosage
mg/kg
Average weight of animals
g
Dosing volume per animal
ul
Number of animals
Step Two: Enter the in vivo formulation
% DMSO
%
% Tween 80
% ddH2O
Calculate Reset

TargetMolCalculator

Molarity Calculator
Dilution Calculator
Reconstitution Calculation
Molecular Weight Calculator
=
X
X

Molarity Calculator allows you to calculate the

  • Mass of a compound required to prepare a solution of known volume and concentration
  • Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Concentration of a solution resulting from a known mass of compound in a specific volume
See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

X
=
X

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

=
/

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

BMS-599626 714971-09-2 Angiogenesis JAK/STAT signaling MAPK Tyrosine Kinase/Adaptors Src HER MEK EGFR antitumor Epidermal growth factor receptor Sal2 inhibit cells ErbB-1 AC-480 proliferation KPL4 AC480 GEO AC 480 Inhibitor HER1 cancer autophosphorylation BMS 599626 selective BMS599626 inhibitor

 

TargetMol