product name XMD17-109
Description: XMD17-109 is a novel, potent, and specific inhibitor of ERK-5 with an EC50 value of 4.2 μM in HEK293 cells. XMD17-109 is capable of inhibiting the ERK5 autophosphorylation in cells. Through intravenous injection and oral delivery of XMD17-109 in mice, the pharmacokinetic properties of this compound are as bellows: the T1/2 is 8.2 h, the plasma clearance is 8.64 mL/min/Kg, the AUC of oral delivery is 15745 h*ng/mL and the oral bioavailability is 90%.
References: Eur J Med Chem. 2013;70:758-67.
638.81
Formula
C36H46N8O3
CAS No.
1435488-37-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (156.5 mM)
Water: <1 mg/mL
Ethanol: 100 mg/mL (156.5 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/1941543
| In Vitro |
In vitro activity: XMD17-109 potently inhibits ERK5 biochemically with an IC50 of 162 nM and in cells with a cellular EC50 for inhibiting epidermal growth factor induced ERK5 autophosphorylation of 0.09 μM Kinase Assay: Kinase activity was determined in an assay volume of 40 μL in kinase buffer (50 mM Tris–HCl, pH 7.5, 0.1 mM EGTA, 1 mM 2-mercaptoethanol) containing 200 ng of pure active ERK5 and the indicated amount of inhibitor. Reaction started by adding 10 mM magnesium acetate, and 50 μM [γ-32P]-ATP (500 cpm/pmol) and 250 μM PIMtide (ARKKRRHPSGPPTA) as substrates. Assays were carried out for 20 min at 30 °C, terminated by applying the reaction mixture onto p81 paper and the incorporated radioactivity measured as described previously. Cell Assay: HeLa cells were serum starved overnight followed by treatment with inhibitors for 1 h. Cells were then stimulated with EGF (20 ng/mL) for 17 min and harvested in RIPA buffer (1× PBS, 1% NP40, 0.5% sodium deoxycholate, 0.1% SDS, 0.1 mg/ml PMSF and 1 mM sodium orthovanadate). Proteins from total cell lysates were resolved by 6% sodium dodecyl sulfate (SDS)-poly-acrylamide gel electrophoresis (PAGE), transferred to nitrocellulose membrane, blocked in 5% nonfat milk, and blotted with anti-ERK5 antibody. |
|---|---|
| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Eur J Med Chem. 2013;70:758-67. |
