AZD8330MEK 1/2 inhibitor CAS# 869357-68-6 |
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Quality Control & MSDS
3D structure
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| Cas No. | 869357-68-6 | SDF | Download SDF |
| PubChem ID | 16666708 | Appearance | Powder |
| Formula | C16H17FIN3O4 | M.Wt | 461.23 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | ARRY-424704; ARRY-704; AZD8330 | ||
| Solubility | DMSO : ≥ 100 mg/mL (216.81 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxopyridine-3-carboxamide | ||
| SMILES | CC1=CC(=C(N(C1=O)C)NC2=C(C=C(C=C2)I)F)C(=O)NOCCO | ||
| Standard InChIKey | RWEVIPRMPFNTLO-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C16H17FIN3O4/c1-9-7-11(15(23)20-25-6-5-22)14(21(2)16(9)24)19-13-4-3-10(18)8-12(13)17/h3-4,7-8,19,22H,5-6H2,1-2H3,(H,20,23) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | AZD8330 is a novel, selective, non-ATP competitive inhibitor of MEK 1/2 with an IC50 value of 7 nM. | |||||
| Targets | ERK phosphorylation | MEK1/2 | ||||
| IC50 | 0.4 nM | 7 nM | ||||
AZD8330 Dilution Calculator
AZD8330 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.1681 mL | 10.8406 mL | 21.6812 mL | 43.3623 mL | 54.2029 mL |
| 5 mM | 0.4336 mL | 2.1681 mL | 4.3362 mL | 8.6725 mL | 10.8406 mL |
| 10 mM | 0.2168 mL | 1.0841 mL | 2.1681 mL | 4.3362 mL | 5.4203 mL |
| 50 mM | 0.0434 mL | 0.2168 mL | 0.4336 mL | 0.8672 mL | 1.0841 mL |
| 100 mM | 0.0217 mL | 0.1084 mL | 0.2168 mL | 0.4336 mL | 0.542 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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AZD8330 is an orally active and selective MEK1/2 inhibitor with an IC50 of 7 nM. The inhibition of MEK1/2 by this component results in inhibition of growth factor-mediated cell signaling and tumor cell proliferation.
MEK, also known as MAP kinase kinase (MAP2K), is a kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK). The activation of MAPK signaling pathway was shown to be involved in regulation of various cell processes including cell proliferation, differentiation, apoptosis, metabolism and inflammation.
AZD8330 treatment was shown to cause cell apoptosis by suppressing the activation of ERK1/2 signal transduction pathway in Burkitt's lymphoma cell line Raji cells, which is in a dose and time dependent manner [1].
Recently, a large phase I trial of 82 patients with advanced tumor malignancies was conducted to define the maximum tolerated dose (MTD) and assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8330. The MTD of this product was determined as 40mg/day [2].
References:
1. Feng K, Wang C, Zhou H, Yang J, Dong L, Zhou K, et al. [Effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism]. Zhonghua Xue Ye Xue Za Zhi 2015,36:148-152.
2. Cohen RB, Aamdal S, Nyakas M, Cavallin M, Green D, Learoyd M, et al. A phase I dose-finding, safety and tolerability study of AZD8330 in patients with advanced malignancies. Eur J Cancer 2013,49:1521-1529.
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[Effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism].[Pubmed:25778893]
Zhonghua Xue Ye Xue Za Zhi. 2015 Feb;36(2):148-52.
OBJECTIVE: To investigate the effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism. METHODS: Raji cells were treated with different concentrations of AZD8330. CCK-8 was used to detect the cell viability. The apoptosis rate of Raji cells was detected by flow cytometry using Annexin V/PI-staining. Real-time PCR was used to assess the expression of Bcl-2, Bcl-xl, caspase-3 and VEGF genes. The protein expression level of Bcl-2, Bcl-xl, caspase-3 and p-ERK1/2 was tested with Western blot. RESULTS: The cell survival rate decreased to(62.09+/-0.86)%,(50.06+/-1.33)% and (39.13+/-2.34)% respectively after cells were treated with AZD8330 at 1.00 mumol/L in vitro for 24 h, 48 h and 72 h, and statistically significant differences were observed in groups with different time of treatment(P<0.05). Apoptosis of cells treated with AZD8330 at 0.10, 1.00, 10.00 mumol/L in vitro for 24 h, 48 h and 72 h was analyzed, and the statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). AZD8330 induced Raji cell apoptosis and upregulated expression of Bcl-2, Bcl-xl, VEFG and decreased the expression of caspase-3 in a dose and time dependent manner, and statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). At the same time, the Bcl-2, Bcl-xl and p-ERK1/2 proteins expression is suppressed obviously, but the expression of caspase-3 protein increased. CONCLUSION: AZD8330 induces cell apoptosis by down-regulating the activation of ERK1/2 signal transduction pathway in Burkitt's lymphoma cell line Raji cells in a dose and time dependent manner.
A phase I dose-finding, safety and tolerability study of AZD8330 in patients with advanced malignancies.[Pubmed:23433846]
Eur J Cancer. 2013 May;49(7):1521-9.
OBJECTIVE: This is the first clinical study of the MEK1/2 inhibitor AZD8330 (ARRY-424704). This phase I study defined the maximum tolerated dose (MTD) and assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8330 in patients with advanced malignancies. METHODS: Patients with refractory cancer or cancer with no standard therapy received either once-daily (OD) or twice-daily (BID) oral AZD8330 on day 1 followed by a 7-day washout period and continuous dosing from day 8. The starting dose was 0.5 mg with dose escalations in subsequent cohorts until a non-tolerated dose was reached. RESULTS: Eighty-two patients received AZD8330 across 11 cohorts. The most frequent AZD8330-related adverse events were acneiform dermatitis (13/82, 16%), fatigue (11/82, 13%), diarrhoea (11/82, 13%) and vomiting (9/82, 11%). Four patients experienced dose-limiting toxicities: mental status changes (40 mg OD; 2/9 patients and 60 mg OD; 1/3) and rash (20 mg BID; 1/9). The MTD was defined as 20mg BID. AZD8330 exposure increased approximately proportionally with dose across the dose range 0.5-60 mg OD. Dose-dependent modulation of phosphorylated ERK in peripheral blood mononuclear cells (PBMCs) was observed at doses >/=3 mg. One patient had a partial response and thirty-two (39%) had stable disease, with a duration >3 months in 22 patients, assessed by Response Evaluation Criteria in Solid Tumors. CONCLUSION: AZD8330 has a manageable toxicity profile at the MTD of 20 mg BID, and target inhibition was confirmed in PBMCs. One patient with malignant melanoma had a partial response.
[Effect of AZD8330 on proliferation and apoptosis of multiple myeloma cells].[Pubmed:25338579]
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Oct;22(5):1311-5.
This study was aimed to investigate the effect of MEK inhibitor AZD8330 on proliferation and apoptosis of multiple myeloma IM9 and NCI-H929 cell lines and its possible mechanism. These two cell line cells were exposed to different concentrations of AZD8330 for 48 h. The CCK-8 assay was used to detect cell viability and the IC50 value at 48 h. These above-mentioned IM9 and NCI-H929 cells were treated with 5,10 and 100 nmol/L of AZD8330, then the change of cell cycle was analysed by flow cytometry with PI staining. The Wester blot was used to detect the expression levels of cyclin D and cyclin E, and multiple myeloma cells were treated with 10, 100, 1000 and 2000 nmol/L of AZD8330, the AnnexinV/7-AAD double staining was used to analyse cell apoptosis and the Western blot was used to detect the expression level of caspase-3. The results showed that AZD8330 could significantly inhibit the cell viability of IM9 and NCI-H929 cell lines in a time-and dose-dependent manner, the IC50 value (48 h) of IM9 and NCI-H929 were 19.88 +/- 2.7 nmol/L and 29.3 +/- 2.03 nmol/L respectively, these two cell lines were arrested on G1 phase of cell cycle, the apoptosis cells increased along with enhancement of AZD8330 concentration, and the expression level of cleaved caspase-3 protein was up-regulated. It is concluded that AZD8330 can efficiently inhibit the proliferation of NCI-H929 and IM9 cell lines, and induce apoptosis, suggesting that the AZD8330 may be a potential chemotherapeutic candidate for multiple myeloma therapy.
