Name: AC480 (BMS-599626)
Brand: Selleck Chemicals
SKU: S1056
Rating: 5 (10 reviews)

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Quality Control

Batch: Purity: 99.08%

99.08

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 c-Kit
Other HER2 Inhibitors	CP-724714 Sapitinib (AZD8931) Mubritinib (TAK 165) Tyrphostin AG 879 HER2-Inhibitor-1 TAS0728 Zongertinib

Chemical Information, Storage & Stability

Molecular Weight	530.55	Formula	C₂₇H₂₇FN₈O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	714971-09-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=C2C(=NC=NN2C=C1NC(=O)OCC3COCCN3)NC4=CC5=C(C=C4)N(N=C5)CC6=CC(=CC=C6)F

Solubility

In vitro
Batch:

DMSO : 113 mg/mL (212.98 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 20 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (56.55mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.

Mechanism of Action

Targets/IC₅₀/Ki	HER1 20 nM HER2 30 nM HER4 190 nM
In vitro	AC480 (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. It also inhibits the related receptor HER4, but with reduced potency with IC50 of 190 nM. This compound inhibits the proliferation of tumour 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 tumour cell line A2780 and MRC5 fibroblasts, neither of which expresses HER1 or HER2, are not inhibited significant by it. A recent study shows that it significantly enhances the radiosensitivity of HN-5 cells expressing both EGFR and Her2 cell, by promoting cycle redistribution and inhibiting DNA repair.
Kinase Assay	Protein kinase assays
Kinase Assay	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 Protein Tyrosine Kinase 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 AC480 (BMS-599626).
In vivo	AC480 (BMS-599626) yields a potent anti-tumour activity in a human breast tumour KPL-4 xenograft at its maximum tolerated dose of 180 mg/kg, and also has similar anti-tumour activity in other HER2 amplified xenograft models, as well as other HER1-overexpressing xenograft models. In vivo, oral administration of this compound results in a dose-dependent inhibition of Sal2 tumour growth at doses ranging from 60 mg/kg to 240 mg/kg.
References	[1] https://pubmed.ncbi.nlm.nih.gov/17062696/ [2] https://pubmed.ncbi.nlm.nih.gov/20119866/ [3] https://pubmed.ncbi.nlm.nih.gov/18765823/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01245543	Withdrawn	Solid Tumors	Daiichi Sankyo	November 2010	Phase 1
NCT00979173	Completed	Glioma	Annick Desjardins\|Ambit Biosciences Corporation\|Duke University	November 2009	Phase 1
NCT00093730	Completed	Unspecified Adult Solid Tumor Protocol Specific	Jonsson Comprehensive Cancer Center\|National Cancer Institute (NCI)	August 2004	Phase 1
NCT00095537	Completed	Cancer\|Metastases	Bristol-Myers Squibb	March 2004	Phase 1

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AC480 (BMS-599626) HER2 inhibitor

Chemical Structure

Molecular Weight: 530.55