XMD17-109

A selective ERK5 inhibitor

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库存: 现货

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5mg

￥887.00

710.00

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25mg

￥3100.00

2480.00

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100mg

￥5900.00

4720.00

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货号: ajci9624
CAS: 1435488-37-1
别名: XMD17 109
分子式: C36H46N8O3
分子量: 638.8
纯度: >98%
溶解度: ≥ 31.95 mg/mL in DMSO, ≥ 86.6 mg/mL in EtOH
储存: Store at -20°C
库存: 现货

Background

XMD17-109 is a new inhibitor of ERK5, IC50 value in HeLa cell is 0.09 ± 0.03 μM, and in vitro, Enzymatic IC50 value is 0.162 ± 0.006 μM.

XMD17-109 is capable of inhibiting the ERK5 autophosphorylation in cells.[1]

Through intravenous injection and oral delivery of XMD17-109 in mice, the pharmacokinetic properties of this compound?are as bellows: the T1/2 (half time)?is 8.2?h, the plasma clearance is 8.64 mL/min/Kg (data of intravenous injection), the AUC (area under the curve) of oral delivery is 15745?h*ng/mL and the oral bioavailability is 90%.

Reference:
1.? Deng, X., et al., Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones. European Journal of Medicinal Chemistry, 2013. 70: p. 758-767.

Protocol

Cell experiment:

HeLa cells are maintained in DMEM supplemented with 10% FBS, 2 mM?l-glutamine, 50 U/mL penicillin G, and 50 μg/mL streptomycin. Before use HeLa cells are serum starved for 16 h in DMEM supplemented with 2 mM?l-glutamine, 50 U/mL penicillin G, and 50 μg/mL streptomycin. HeLa cells are then incubated with ERK5-IN-1 at the indicated concentrations for 1 h prior to stimulation with 0.5mol/Lsorbitol for 30 min. Cells are lysed in Triton lysis buffer (50 mM Tris-HCl, pH 7.5, 1 mM EGTA, 1 mM EDTA, 1 mM sodium orthovanadate, 50 mM sodium fluoride, 1 mM sodium pyrophosphate, 0.27mol/Lsucrose, 1 μM microcystin-LR, 1% (v/v) Triton X-100, 0.1% (v/v) 2-mercaptoethanol) and 20 μg of protein loaded per well. Samples are run on 8% polyacrylamide gels using standard methods. Proteins are transferred onto nitrocellulose membranes and specific proteins detected by immunoblotting.

参考文献:

[1]. Deng X, et al. Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones. Eur J Med Chem. 2013;70:758-67.
[2]. Elkins, Jonathan M., et al. X-ray Crystal Structure of ERK5 (MAPK7) in Complex with a Specific Inhibitor. Journal of Medicinal Chemistry (2013), 56(11), 4413-4421.
[3]. Wilhelmsen K, et al. Extracellular signal-regulated kinase 5 promotes acute cellular and systemic inflammation. Sci Signal. 2015 Aug 25;8(391):ra86.