AC480 (BMS-599626)

Name: AC480 (BMS-599626)
Brand: Selleck Chemicals
SKU: S1056
Rating: 5 (7 reviews)

For research use only.

Catalog No.S1056

7 publications

Molecular Weight(MW): 530.55

AC480 (BMS-599626) is a selective and efficacious inhibitor of HER1 and HER2 with IC50 of 20 nM and 30 nM, ~8-fold less potent to HER4, >100-fold to VEGFR2, c-Kit, Lck, MET etc. Phase 1.

Selleck's AC480 (BMS-599626) has been cited by 7 publications

Cancer Cell, 2012, 22(5):656-67

PubMed: 23153538 ( click the link to review the publication )

Genome Med, 2020, 18;12(1):17

PubMed: 32070411 ( click the link to review the publication )

Asian J Androl, 2016, 10.4103/1008-682X

PubMed: 27232851 ( click the link to review the publication )

Oncotarget, 2016, 7(24):36956-36970

PubMed: 27172793 ( click the link to review the publication )

Genes Cancer, 2014, 5(7-8):261-72

PubMed: 25221644 ( click the link to review the publication )

Head Neck, 2014, 10.1002/hed.23822.?

PubMed: 24986420 ( click the link to review the publication )

J Cell Mol Med, 2013, 17(5):648-56

PubMed: 23601074 ( click the link to review the publication )

5 Customer Reviews

RCH-ACV cells were treated with ponatinib(50 nM), PCI-32765(50 nM), or BMS-599626(500 nM) over a time course, and whole-cell extracts were subjected to immunoblot analysis

for total or phospho-AKT.

Cancer Cell 2012 22(5), 656-667 . AC480 (BMS-599626) purchased from Selleck.

Co-treatments of PI-103 and EGFR inhibitors enhance cytotoxicity in SUM149PT cells. Cells were treated with 0.3 uM of PI-103 in combination with different concentrations (0.1 and 1 uM) of EGFR inhibitors (BMS-599626) for -72 hrs. Cell viability was measured by MTT assay as described in Materials and methods. Data from two independent experiments performed in triplicate are shown as mean+SEM. *P < 0.05; **P < 0.01; ***P < 0.001.

J Cell Mol Med 2013 17(5), 648-56. AC480 (BMS-599626) purchased from Selleck.
Breast cancer cells were pretreated with 100ng/ml EGF for 15 min and then treated with the indicated concentrations of BMS-599626.

2010 Dr. Zhang of Tianjin Medical University. AC480 (BMS-599626) purchased from Selleck.

AC480, a Her-2 inhibitor, blocked the effect of PlncRNA-1 in RWPE-1 cells. （a and b） After PlncRNA-1 overexpression in RWPE-1 cells, the number of cells in G2/M phase decreased. After addition of the Her-2 inhibitor AC480, the number of cells in G2/M phase increased again. （c） CyclinD1 expression in RWPE-1 cells was increased after the overexpression of PlncRNA-1. After addition of the Her-2 inhibitor AC480, the expression of cyclinD1 in RWPE-1 cells was decreased again.

Asian J Androl, 2017, 19(4):453-457. AC480 (BMS-599626) purchased from Selleck.
Synergistic effects of foretinib and HER2 inhibitors on the cytotoxicities of ESCC. Cell viability of ESCC cells treated by 1 μM of foretinib, or 1 μM of HER2 inhibitors, or foretinib plus HER2 inhibitor. The HER2 inhibitors included 1 μM of lapatinib B. or 1 μM of afatinib C. or 1 μM of AC480 (D)

Oncotarget, 2016, 7(24):36956-36970. AC480 (BMS-599626) purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description

AC480 (BMS-599626) is a selective and efficacious inhibitor of HER1 and HER2 with IC50 of 20 nM and 30 nM, ~8-fold less potent to HER4, >100-fold to VEGFR2, c-Kit, Lck, MET etc. Phase 1.

Targets

HER1 ^[1] ()	HER2 ^[1]	HER4 ^[1]
20 nM	30 nM	190 nM

In vitro

BMS-599626 also inhibits the related receptor HER4, but with reduced potency with IC50 of 190 nM. BMS-599626 is identified as an ATP-competitive inhibitor for HER1 and as an ATP-noncompetitive inhibitor for HER2 with K_i of 2 nM and 5 nM, respectively. BMS-599626 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 of 0.24 μM, 0.31 μM, 0.45 μM, 0.38μM, 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. While the proliferation of the ovarian tumor cell line A2780 and MRC5 fibroblasts, neither of which expresses HER1 or HER2, are not inhibited significant by BMS-599626. ^[1] A recent study shows that BMS-599626 significantly enhances the radiosensitivity of HN-5 cells expressing both EGFR and Her2 cell, by promoting cycle redistribution and inhibiting DNA repair. ^[2]

In vivo

In vivo, oral administration of BMS-599626 results in a dose-dependent inhibition of Sal2 tumor growth at doses ranging from 60 mg/kg to 240 mg/kg, yielding a potent antitumor activity in a human breast tumor KPL-4 xenograft at its maximum tolerated dose of 180 mg/kg, and also has similar antitumor activity in other HER2 amplified xenograft models, as well as other HER1-overexpressing xenograft models. ^[1]

Protocol

Kinase Assay:^[1]	- Collapse 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:^[1]	- Collapse Cell lines: Sal2, BT474, N87, KPL-4, HCC202, HCC1954, HCC1419, AU565, ZR-75-30, MDA-MB-175, GEO, PC9, A2780 and MRC5 Concentrations: 0-10 μM Incubation Time: 72 hours Method: 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)
Animal Research:^[1]	- Collapse Animal Models: 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 are maintained and passaged in athymic female nude mice. Dosages: ≤240 mg/kg Administration: Administered via p.o. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	113 mg/mL (212.98 mM)
	Ethanol	20 mg/mL (37.69 mM)
	Water	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

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download AC480 (BMS-599626) SDF

Molecular Weight	530.55
Formula	C₂₇H₂₇FN₈O₃
CAS No.	714971-09-2
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=C2[N](C=C1NC(=O)OCC3COCCN3)N=CN=C2NC4=CC5=C(C=C4)[N](CC6=CC=CC(=C6)F)N=C5

In vivo Formulation Calculator (Clear solution)

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

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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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，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.

Bio Calculators

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

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Molecular Weight Calculator

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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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

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Features:A potent EGFR tyrosine kinase inhibitor.

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AC480 (BMS-599626)