BMS-599626 Hydrochloride
Based on 3 publication(s) in Google Scholar
BMS-599626 Hydrochloride (AC480 Hydrochloride) is a selective and orally bioavailable HER1 and HER2 inhibitor, with IC50s of 20 and 30 nM, respectively. BMS-599626 Hydrochloride displays ~8-fold less potent to HER4 (IC50=190 nM), >100-fold to VEGFR2, c-Kit, Lck, MEK. BMS-599626 Hydrochloride inhibits tumor cell proliferation, and has potential to increase tumor response to radiotherapy.
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- Pureté : 98.90%
- CAS No.: 873837-23-1
- Formule: C27H28ClFN8O3
- Masse moléculaire:567.01
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Stockage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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BMS-599626HER1/2 Inhibitor
Publications Citing Use of MedChemExpress (MCE) BMS-599626 Hydrochloride
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Activité biologique
Description
In Vitro
BMS-599626 Hydrochloride inhibits the proliferation of tumor cells that are dependent on HER1/HER2 signaling.BMS-599626 Hydrochloride (0.03-8 μM; 1 huors) results in the inhibition of receptor autophosphorylation, as well as MAPK phosphorylation, with IC50s of 0.3 and 0.22 μM, respectively, in Sal2 cells which express a CD8HER2 fusion protein[1].
BMS-599626 Hydrochloride abrogates HER1 and HER2 signaling and inhibited the proliferation of tumor cell lines that are dependent on these receptors, with IC50s in the range of 0.24 to 1 μM.In GEO cells, HER1 phosphorylation is stimulated by treatment with EGF and is inhibited by BMS-599626 Hydrochloride (IC50=0. 75 μM).There is also nearly complete inhibition of EGF-dependent MAPK (0. 8 μM) but only partial inhibition of AKT signaling.The latter likely reflects the activation of AKT by multiple upstream signals.Treatment of N87 cells with BMS-599626 Hydrochloride leads to the inhibition of HER2 (0. 38 μM), which is expressed to a high level because of gene amplification, as well as MAPK and AKT phosphorylation (0.35 μM for both)[1].
At the molecular level, in HN-5 cells the agent (BMS-599626 Hydrochloride) inhibits the expression of pEGFR, pHER2, cyclins D and E, pRb, pAkt, pMAPK, pCDK1 and 2, CDK 6, and Ku70 proteins. BMS-599626 Hydrochloride also induced accumulation of cells in the G1 cell cycle phase, inhibited cell growth, enhanced radiosensitivity, and prolonged the presence of γ-H AX foci up to 24 h after radiation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
BMS-599626 Hydrochloride treatment results in the inhibition of GEO xenograft tumor growth when given once daily for 14 days. In addition to efficacy in the Sal2, GEO, and KPL4 models, BMS-599626 has similar antitumor activity in other HER2 amplified xenograft models including the BT474 breast and N87 gastric tumors, as well as other HER1-overexpressing non-small-cell lung tumors (A549 and L2987)[1].
BMS-599626 Hydrochloride given before and during irradiation improved the radioresponse of HN5 tumors in vivo[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Athymic female nude mice (nu/nu mice, Sal2 tumor model)[1]
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Dosage:60, 120, 240 mg/kg
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Administration:Oral; daily for 14 days
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Result:Resulted in a dose-dependent inhibition of Sal2 tumor growth.
Chemical Information
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CAS No. 873837-23-1
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Appearance Solid
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Masse moléculaire 567.01
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Formule C27H28ClFN8O3
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Color White to off-white
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SMILES
O=C(OC[C@H]1NCCOC1)NC2=CN(C3=C2C)N=CN=C3NC4=CC5=C(C=C4)N(CC6=CC(F)=CC=C6)N=C5.Cl
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Synonyms
AC480 Hydrochloride
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (3)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Life Sci
Skp2 promotes APL progression through the stabilization of oncoprotein PML-RARα and the inhibition of JunB expression. [Abstract]2021 Dec 16;289:120231. PMID: 34921867 -
BMC Pulm Med
The combination therapy of isomucronulatol 7-O-beta-glucoside (IMG) and CEP-9722 targeting ferroptosis-related biomarkers in non-small cell lung cancer (NSCLC). [Abstract]2023 May 11;23(1):162. PMID: 37165402
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (176.36 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.41 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.41 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (276 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Wong TW, et al. Preclinical antitumor activity of BMS-599626, a pan-HER kinase inhibitor that inhibits HER1/HER2 homodimer and heterodimer signaling. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6186-93. [Content Brief]
[2]. Torres MA, et al. AC480, formerly BMS-599626, a pan Her inhibitor, enhances radiosensitivity and radioresponse of head and neck squamous cell carcinoma cells in vitro and in vivo. Invest New Drugs. 2011 Aug;29(4):554-61. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.7636 mL | 8.8182 mL | 17.6364 mL | 44.0909 mL |
| 5 mM | 0.3527 mL | 1.7636 mL | 3.5273 mL | 8.8182 mL | |
| 10 mM | 0.1764 mL | 0.8818 mL | 1.7636 mL | 4.4091 mL | |
| 15 mM | 0.1176 mL | 0.5879 mL | 1.1758 mL | 2.9394 mL | |
| 20 mM | 0.0882 mL | 0.4409 mL | 0.8818 mL | 2.2045 mL | |
| 25 mM | 0.0705 mL | 0.3527 mL | 0.7055 mL | 1.7636 mL | |
| 30 mM | 0.0588 mL | 0.2939 mL | 0.5879 mL | 1.4697 mL | |
| 40 mM | 0.0441 mL | 0.2205 mL | 0.4409 mL | 1.1023 mL | |
| 50 mM | 0.0353 mL | 0.1764 mL | 0.3527 mL | 0.8818 mL | |
| 60 mM | 0.0294 mL | 0.1470 mL | 0.2939 mL | 0.7348 mL | |
| 80 mM | 0.0220 mL | 0.1102 mL | 0.2205 mL | 0.5511 mL | |
| 100 mM | 0.0176 mL | 0.0882 mL | 0.1764 mL | 0.4409 mL |
BMS-599626 Hydrochloride Related Classifications
HY-12010 Related Classifications
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