-20℃ 3 years powder
-80℃ 2 years in solvent
BMS-599626 (AC480) is a selective inhibitor of HER1 and HER2 (IC50s: 20 nM and 30 nM), ~8-fold less potent to HER4, >100-fold to Lck, VEGFR2, c-Kit, MET, etc.
|1 mg||In stock||50.00|
|5 mg||In stock||126.00|
|25 mg||In stock||419.00|
|50 mg||In stock||672.00|
|1 mL * 10 mM (in DMSO)||In stock||320.00|
|Description||BMS-599626 (AC480) is a selective inhibitor of HER1 and HER2 (IC50s: 20 nM and 30 nM), ~8-fold less potent to HER4, >100-fold to Lck, VEGFR2, c-Kit, MET, etc.|
|Targets&IC50||HER1 :ic50 20 nM (cell free), HER2 :ic50 30 nM (cell free), HER3 :ic50 190 nM (cell free),|
|In vivo||At 60 mg/kg, BMS-599626 achieved a significant delay of tumor growth in the course of treatment, but tumor growth resumed following the cessation of treatment. Higher doses of BMS-599626 provided more sustained inhibition of tumor growth, but in all cases, tumor growth resumed on treatment cessation. In a once-daily regimen, the maximum tolerated dose for 14 days of dosing of BMS-599626 was 240 mg/kg .|
|Kinase Assay||The entire cytoplasmic sequences of HER1, HER2, and HER4 were expressed as recombinant proteins in Sf9 insect cells. HER1 and HER4 were expressed as fusion proteins with glutathione-S-transferase and were purified by affinity chromatography on glutathione-S-Sepharose. HER2 was subcloned into the pBlueBac4 vector and expressed as an untagged protein using an internal methionine codon for translation initiation. The truncated HER2 protein was isolated by chromatography on a column of DEAE-Sepharose equilibrated in a buffer that contained 0.1 mol/L NaCl, and the recombinant protein was eluted with a buffer containing 0.3 mol/L NaCl. For the HER kinase assays, reaction volumes were 50 μL and contained 10 ng of glutathione-S-transferase fusion protein or 150 ng of partially purified HER2. The mixtures also contained 1.5 μmol/L poly(Glu/Tyr) (4:1), 1 μmol/L ATP, 0.15 μCi [γ-33P]ATP, 50 mmol/L Tris-HCl (pH 7.7), 2 mmol/L DTT, 0.1 mg/mL bovine serum albumin, and 10 mmol/L MnCl2. Reactions were allowed to proceed at 27°C for 1 hour and were terminated by the addition of 10 μL of a stop buffer (2.5 mg/mL bovine serum albumin and 0.3 mol/L EDTA), followed by a 108-μL mixture of 3.5 mmol/L ATP and 5% trichloroacetic acid. Acid-insoluble proteins were recovered on GF/C Unifilter plates with a Filtermate harvester. Incorporation of radioactive phosphate into the poly(Glu/Tyr) substrate was determined by liquid scintillation counting. Percent inhibition of kinase activity was determined by nonlinear regression analyses and data were 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 were also assayed using poly(Glu/Tyr) as a substrate .|
All cell lines were maintained in RPMI 1640 supplemented with 10% fetal bovine serum, 100 units/mL penicillin, and 100 μg/mL streptomycin. Cells were plated at 1,000 per well in 96-well plates and were cultured for 24 hours before test compounds were added. Compounds were diluted in culture medium such that the final concentration of DMSO never exceeded 1%. Following the addition of compounds, the cells were cultured for an additional 72 hours before cell viability was 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 was 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 was used to measure proliferation of these cell lines. Cells were plated in 96-well plates and treated with compounds as above. At the end of the 72-hour incubation, cells were pulsed with [3H]thymidine (0.4 μCi/well) for 3 hours before they were harvested. Cells were digested with 2.5% trypsin for 10 minutes at 37°C and were harvested by filtration using a Packard Filtermate Harvester and GF/C Unifilter plates. Incorporation of radioactive thymidine into nucleic acids was determined by liquid scintillation counting .
|Synonyms||AC480 dihydrochloride , AC480 dihydrochloride|
-20℃ 3 years powder
-80℃ 2 years in solvent
DMSO: 95 mg/mL (167.55 mM)
Water: 3 mg/mL
( < 1 mg/ml refers to the product slightly soluble or insoluble )
Safe and effective drug dosing is necessary, regardless of its purpose of administration. Learn More
Answers to questions you may have can be found in the Inhibitor Handling Instructions. Topics include how to prepare stock solutions, how to store Products, and issues that need special attention for cell-based assays and animal experiments.