ARRY-380 (Synonyms: ARRY380; ARRY 380) |
| Catalog No.GC12478 |
ARRY-380, an inhibitor of EGFR (ErbB1), is extracted from patent WO2015153959A2, compound 249. ARRY-380 is a potent, selective, ATP-competitive, orally active inhibitor of HER2.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 937265-83-3
Sample solution is provided at 25 µL, 10mM.
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IC50: 8 nM (HER2)
HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. Amplification or overexpression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. ARRY-380 is an orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity.
In vitro: ARRY-380 is reported to be a reversible, ATP-competitive inhibitor with nanomolar activity against HER2 enzyme. In cell-based assays, ARRY-380 is ~500-fold selective for HER2 vs. EGFR and is equipotent against truncated p95-HER2 [1].
In vivo: ARRY-380 treatment significantly enhances survival in two ErbB2 driven intracranial tumor xenograft models, with superior activity compared to other ErbB2 agents in these studies. Additionally, ARRY-380 has demonstrated durable clinical activity in heavily pre-treated patients with ErbB2+ MBC. These preclinical and clinical data suggest that ARRY-380 may provide benefit to patients with ErbB2+ MBC with brain metastases. These preclinical and clinical data suggest that ARRY-380 may provide benefit to patients with ErbB2+ MBC with brain metastases and warrants further study [2].
Clinical trial: In a phase 1 clinical trial, 15 patients have been treated in 5 dosing cohorts at doses of 25 to 300 mg BID. No DLTs have been observed and drug-related adverse events have included Grade 1 nausea, rash and fatigue and Grade 2 fatigue in 2 patients at the 200 mg BID dose level. Preliminary PK analyses indicate a trend for increasing Cmax and AUC with increasing dose, a median Tmax of 2 hours and a mean t1/2 of 4.6 hours across all cohorts. Two patients with HER2+ breast cancer have had stable disease for ≥ 4 months with no significant toxicity. One of these two patients had a notable reduction in liver metastases (28%) after 2 cycles of ARRY-380 and is currently on study.These findings indicate ARRY-380 has demonstrated an acceptable safety and PK profile and preliminary signs of clinical benefit. Dose escalation continues to determine the MTD [3].
References:
[1] S. L. Moulder, V. Borges, S. K. L. Chia, T. Baetz, E. Barrett, J. Garrus, K. Guthrie, C. Kass, E. Laird, J. Lyssikatos, F. Marmsater, E. Wallace. ARRY-380, a Selective HER2 Inhibitor: From Drug Design to Clinical Evaluation. Poster of AACR-NCI-EORTC, Nov 12-16, 2011, San Francisco, CA.
[2] Victoria Dinkel, Deborah Anderson, Shannon Winski, Jim Winkler, Kevin Koch and Patrice Lee. ARRY-380, a potent, small molecule inhibitor of ErbB2, increases survival in intracranial ErbB2+ xenograft models in mice. Poster available at www.arraybiopharma.com
[3] S. Chia, T. Baetz, S. D'Aloisio, G. Fernetich, B. Freeman, E. Barrett, C. Kass, J. Kang, B. Sajan, S. Moulder, and J. Garrus. A Phase 1 Study To Assess the Safety, Tolerability and Pharmacokinetics of ARRY-380 – An Oral Inhibitor of HER2. Cancer Res 2009;69(24 Suppl):Abstract nr 5111.
| Cell experiment [1]: | |
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Cell lines |
BT474 cells, NIH-3T3 cells |
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Preparation method |
Soluble in DMSO >28.5mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
N/A |
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Applications |
ARRY-380 is an orally active, selective, small molecule inhibitor of ErbB2(human epidermal growth factor receptor-2). Its activity (IC50) against ErbB2 enzyme is 14 nM and it inhibits the phosphorylation of ErbB2 in BT474 cells in culture with an IC 50 of 21 nM. ARRY-380 also potently inhibits phosphorylation of AKT(protein kinase B), induces apoptosis and inhibits growth of BT474 cells in vitro. Marked tumor growth inhibition has been demonstrated in NIH-3T3 cells stably transfected with constitutively active ErbB2 kinase (3T3-rErbB2). |
| Clinical experiment [2]: | |
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Disease models |
Patients with HER2-positive cancers (including HER2+MBC(Metastatic Breast Cancer)) |
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Dosage form |
Dose-escalation cohorts(HER2+ cancer): A starting dose of 25 mg BID(twice-daily)was utilized with additional cohorts at planned dose levels of 50, 100, 200, 300, 500, 650 and 800 mg dosing in a fed state in continuous 28-day cycles (600mg BID was the MTD(maximum tolerated dose)) in Cycle 1.expansion cohort(HER2+MBC): 600mg BID in continuous 28-day cycles in Cycle 2. |
|
Application |
ARRY-380 had a lower incidence and severity of diarrhea and rash than that typically associated with current dual HER2/EGFR (Epidermal Growth Factor Receptor) inhibitors and showed notable anti-tumor activity in heavily pretreated HER2+MBC patients, supporting its continued development. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Pheneger, T., et al., In vitro and in vivo activity of ARRY-380: A potent, small molecule inhibitor of ErbB2. Presented at the American Association of Cancer Research 100th Annual Meeting Apr 18-22, 2009; Cancer Res 69 (abstr 1795). [2]. Moulder SL1, Borges VF2, et al, Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC). Clin Cancer Res. 2017 Jul 15;23(14):3529-3536. doi: 10.1158/1078-0432.CCR-16-1496. Epub 2017 Jan 4. | |
| Cas No. | 937265-83-3 | SDF | |
| Synonyms | ARRY380; ARRY 380 | ||
| Chemical Name | 6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]-N-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazolin-4-amine | ||
| Canonical SMILES | CC1=C(C=CC(=C1)NC2=NC=NC3=C2C=C(C=C3)C4=CC=C(O4)CNCCS(=O)(=O)C)OC5=CC6=NC=NN6C=C5 | ||
| Formula | C29H27N7O4S | M.Wt | 569.63 |
| Solubility | ≥ 28.5mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7555 mL | 8.7776 mL | 17.5553 mL |
| 5 mM | 0.3511 mL | 1.7555 mL | 3.5111 mL |
| 10 mM | 0.1756 mL | 0.8778 mL | 1.7555 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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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 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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