AZD8330
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 461.23 |
| Cas No. | 869357-68-6 |
| Formula | C16H17FIN3O4 |
| Synonyms | ARRY-424704; ARRY-704; AZD-8330; ARRY424704; ARRY704; AZD8330 |
| Solubility | ≥23.05 mg/mL in DMSO; insoluble in H2O; ≥46.1 mg/mL in EtOH |
| Chemical Name | 2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxopyridine-3-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC(=C(N(C1=O)C)NC2=C(C=C(C=C2)I)F)C(=O)NOCCO |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
MOS, U2OS, KPD, ZK58, 143b and Saos-2 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0 ~ 1 μM; 72 hrs |
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Applications |
AZD8330 decreased viability of MOS and U2OS cells, and significantly affected 143b cells. In contrast, AZD8330 exhibited no effect on viability of KPD, ZK58 and Saos-2 cells. According to a capase3/7 activity assay, AZD8330 at the concentration of 0.5μM induced apoptosis in MOS and U2OS cells, but not in KPD and ZK58 cells. |
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References: [1]. Zuzanna Baranski, Tijmen H. Booij, Marieke L. Kuijjer, Yvonne de Jong, Anne-Marie Cleton-Jansen, Leo S. Price, Bob van de Water, Judith V. M. G. Bovée, Pancras C.W. Hogendoorn, Erik H.J. Danen. MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation. Genes Cancer. 2015 Nov; 6(11-12): 503–512. |
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| 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 | ||||
Quality Control & MSDS
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Chemical structure
