AZD6244 (ARRY-142886, Selumetinib) is a potent MEK 1/2 inhibitor with GI50 values ranging from 14 to 50 nM. AZD6244 has potential to inhibit proliferation and induce apoptosis and differentiation, but the response varies between different xenografts.
|Cell lines||HT-29, Malme-3M, MIAPaCa-2, SK-MEL-2, SK-MEL-28, BxPC3, BT-474, Zr-75-1, Malme-3|
|Preparation method||Cellular viability assays Cells plated in 96-well plates were incubated with multiple concentrations of compound for 3 days. The number of viable cells was determined using the CellTiter 96 Aqueous Nonradioactive Cell Proliferation Assay (Promega, Madison, WI).|
|Incubation time||3 days|
|Animal models||HT-29 and BxPC3 xenograft|
|Formulation||10% ethanol/10% cremophor EL/80% D5W|
|Dosages||10, 25, 50, or 100 mg/kg BID|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Source||Cell Biol Int (2014). Figure 5. AZD6244|
|Cell Lines||Raji and MOLT-4 cells|
|Incubation Time||48 h|
|Results||Consistent with role in the growth inhibition, silencing of Bim decreases the AZD6244-induced apoptosis (Figure 5D) and abrogates AZD6244 induced G1 arrest (Figure 5E).|
|Source||Cell Biol Int (2014). Figure 1. AZD6244|
|Cell Lines||Raji and MOLT4 cells|
|Incubation Time||48 h|
|Results||AZD6244 significantly blocked ERK phosphorylation in Raji and MOLT4 cells (Figure 1A). AZD6244 significantly inhibited proliferation of both Raji and MOLT4 in a dose-dependent manner (n¼3, P<0.01; Figure 1B).|
Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma.
Yuen et al. Int J Oncol. 2012 Aug;41(2):712-20. PMID: 22641227.
Activity of the MEK inhibitor selumetinib (AZD6244; ARRY-142886) in nasopharyngeal cancer cell lines.
Ma BB et al. Invest New Drugs. 2012 May 8. PMID: 22565394.
Selumetinib (AZD6244; ARRY-142886) in the treatment of metastatic melanoma.
Patel et al. Expert Opin Investig Drugs. 2012 Apr;21(4):531-9. PMID: 22394161.
The MEK1/2 inhibitor, selumetinib (AZD6244; ARRY-142886), enhances anti-tumour efficacy when combined with conventional chemotherapeutic agents in human tumour xenograft models.
Holt et al. Br J Cancer. 2012 Feb 28;106(5):858-66. PMID: 22343622.
MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell carcinoma in a PEA-15-dependent manner in a mouse xenograft model.
Bartholomeusz et al. Mol Cancer Ther. 2012 Feb;11(2):360-9. PMID: 22144664.
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