AZD8330 (ARRY-424704) is a novel, selective, highly efficacious, uncompetitive MEK inhibitor with an IC50 of 7 nM.AZD8330 demonstrates sub-nanomolar potency in mechanistic (pERK) and low to sub-nanomolar potency in functional (proliferation) assays in MEK 1/2 inhibitor sensitive cell lines.
|Cell lines||HT-29, Malme-3M, MIA PaCa-2, BxPC3, BT474, Zr-75-1 and Malme-3 cell lines|
|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 mL/kg and 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||Eur J Cancer (2013). Figure 4. AZD8330|
|Cell Lines||osteosarcoma cell lines|
|Incubation Time||6 h|
|Results||The resistant cell lines KPD, ZK58 and Saos-2 showed no constitutive ERK activation. Exposing MOS, U2OS and 143b to a concentration of 0.5μM of Trametinib, AZD8330 or TAK-733 for 6 hours, led to loss of ERK phosphorylation indicating effective MEK inhibition|
|Related MEK Products|
BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively.
LY2801653 is a potent, orally bioavailable, small-molecule inhibitor of c-MET kinase(Ki= 2 nM).
Refametinib (BAY 86-9766, RDEA119) is a potent, highly selective and ATP non-competitive inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively.
GDC-0973 is a potent, highly selective inhibitor of mitogen-activated protein kinase kinase (MEK1/2).
PD 198306 is a cell-permeable and highly selective MEK inhibitor with IC50 of 8 nM.
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