Size | Price | Stock | Qty |
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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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Other Sizes |
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Purity: ≥98%
AC480 (also known as BMS-599626) is a novel, potent, orally bioavailable, selective and efficacious inhibitor of HER1/2 (human epidermal growth factor receptors) with potential anticancer activity. Its IC50s are 20 nM and 30 nM, respectively, for HER1/2 inhibition. It is less potent against HER4 by about 8 times and less active against VEGFR2, c-Kit, Lck, MET, and other proteins by over 100 times. It has been shown that oral administration of AC480 inhibits the growth of the GEO xenograft tumor, KPL-4 and BT474 breast tumors, N87 gastric tumor, A549 and L2987 non-small-cell lung tumors, and Sal2 tumor in nude mice.
Targets |
HER1 (IC50 = 20 nM); HER2 (IC50 = 30 nM); HER4 (IC50 = 190 nM)
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
In Sf9 insect cells, the full cytoplasmic sequences of HER1, HER2, and HER4 are expressed as recombinant proteins. Glutathione-S-transferase is used to express HER1 and HER4, which are then purified using affinity chromatography on glutathione-S-Sepharose. The pBlueBac4 vector is used to subclone HER2, which is then expressed as an untagged protein with the help of an internal methionine codon (M687) that initiates translation. By using chromatography on a column of DEAE-Sepharose that has been equilibrated in a buffer containing 0.1 M NaCl, the truncated HER2 protein is isolated, and the recombinant protein is eluted using a buffer containing 0.3 M NaCl. Reaction volumes for the HER kinase tests are 50 μL, and the contents include 150 ng of partially purified HER2 or 10 ng of glutathione-S-transferase fusion protein. The mixture additionally contains 50 mM Tris-HCl (pH 7.7), 2 mM DTT, 0.1 mg/mL bovine serum albumin, 10 mM MnCl2, 0.15 μCi [γ-33P]ATP, 1 μM ATP, and 1.5 μM poly(Glu/Tyr) (4:1). The reactions are allowed to continue for one hour at 27°C before being stopped with the addition of 10 μL of a stop buffer (2.5 mg/mL bovine serum albumin and 0.3 M EDTA) and 108 μL of a mixture consisting of 5% trichloroacetic acid and 3.5 mM ATP. Using a Filtermate harvester, acid-insoluble proteins are recovered on GF/C Unifilter plates. Liquid scintillation counting is used to determine whether radioactive phosphate has been incorporated into the poly(Glu/Tyr) substrate. Nonlinear regression analyses are used to calculate the percent inhibition of kinase activity. The data are presented as the inhibitory concentration needed to achieve 50% inhibition in comparison to control reactions (IC50). The averages of three duplicate determinations are called data. Poly(Glu/Tyr) is used as a substrate in the assay of all other tyrosine kinases. The inhibition kinetics of HER1 and HER2 are ascertained in reaction mixtures comprising different quantities of BMS-599626 and ATP.
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Cell Assay |
In RPMI 1640 supplemented with 10% fetal bovine serum, 100 units/mL penicillin, and 100 μg/mL streptomycin, all cell lines are kept alive. Prior to adding BMS-599626, cells are plated in 96-well plates at a density of 1,000 per well and cultured for a full day. BMS-599626 is diluted in culture medium until the final DMSO concentration is less than one percent. The cells are cultured for an additional 72 hours after the addition of BMS-599626, and the CellTiter96 kit is used to measure the conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye in order to determine the viability of the cells. Thymidine uptake assay is used to measure the proliferation of cell lines for which there is no correlation between the number of cells and the metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye. The aforementioned compounds are applied to cells after they have been plated in 96-well plates. After the 72-hour incubation period, cells are harvested after being pulsed with [3H]thymidine (0.4 μCi/well) for three hours. Following ten minutes of 2.5% trypsin digestion at 37 °C, the cells are collected by filtration through the use of GF/C Unifilter plates and a Packard Filtermate Harvester. Liquid scintillation counting is used to measure the amount of radioactive thymidine incorporated into nucleic acids.
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Animal Protocol |
Athymic female nude mice are used to maintain and pass on SAL2 murine salivary gland tumor, N87 human gastric carcinoma, BT474 human breast tumor, A549 human non-small-cell lung tumor, and GEO human colon tumor.
≤240 mg/kg Administered via p.o. |
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References |
Molecular Formula |
C27H27FN8O3
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Molecular Weight |
530.55
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Exact Mass |
530.22
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Elemental Analysis |
C, 61.12; H, 5.13; F, 3.58; N, 21.12; O, 9.05
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CAS # |
714971-09-2
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Related CAS # |
BMS-599626 Hydrochloride;873837-23-1
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Appearance |
Solid powder
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SMILES |
CC1=C2C(=NC=NN2C=C1NC(=O)OC[C@@H]3COCCN3)NC4=CC5=C(C=C4)N(N=C5)CC6=CC(=CC=C6)F
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InChi Key |
LUJZZYWHBDHDQX-QFIPXVFZSA-N
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InChi Code |
InChI=1S/C27H27FN8O3/c1-17-23(34-27(37)39-15-22-14-38-8-7-29-22)13-36-25(17)26(30-16-32-36)33-21-5-6-24-19(10-21)11-31-35(24)12-18-3-2-4-20(28)9-18/h2-6,9-11,13,16,22,29H,7-8,12,14-15H2,1H3,(H,34,37)(H,30,32,33)/t22-/m0/s1
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Chemical Name |
[(3S)-morpholin-3-yl]methyl N-[4-[[1-[(3-fluorophenyl)methyl]indazol-5-yl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamate
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8848 mL | 9.4242 mL | 18.8484 mL | |
5 mM | 0.3770 mL | 1.8848 mL | 3.7697 mL | |
10 mM | 0.1885 mL | 0.9424 mL | 1.8848 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00979173 | Completed | Drug: AC480 | Glioma | Annick Desjardins | November 2009 | Phase 1 |
NCT00095537 | Completed | Drug: panHer | Cancer Metastases |
Bristol-Myers Squibb | March 2004 | Phase 1 |
NCT00093730 | Completed | Drug: BMS-59926 | Unspecified Adult Solid Tumor, Protocol Specific |
Jonsson Comprehensive Cancer Center |
August 2004 | Phase 1 |
NCT00207012 | Completed | Drug: BMS-599626 | HER2 or EGFR Expressing Advanced Solid Malignancies |
Bristol-Myers Squibb | May 2004 | Phase 1 |
NCT01245543 | Withdrawn | Drug: AC480IV Drug: Docetaxel |
Solid Tumors | Daiichi Sankyo, Inc. | November 2010 | Phase 1 |
BMS-599626 inhibits HER1/HER2 heterodimer formation. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6186-93. td> |
Antitumor activity of BMS-599626. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6186-93. td> |
Pharmacokinetics of BMS-599626 and pharmacodynamic assessment of Sal2 tumor inhibition by BMS-599626. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6186-93. td> |