Acumapimod

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Chemical Structure| 836683-15-9 同义名 : BCT197
CAS号 : 836683-15-9
货号 : A324033
分子式 : C22H19N5O2
纯度 : 99%+
分子量 : 385.42
MDL号 : MFCD28902244
存储条件：

Pure form Keep in dark place, sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 p38 mitogen-activated protein kinases (p38 MAPK, p38) consist of 4 subunits: p38α, p38β, p38γ and p38δ. They play a well-recognized role in regulating intracellular signaling transduction in mammalian cells. p38 MAPK induces a variety of intracellular responses associated with neuropathic pain and other chronic pain[2]. Acumapimod（BCT197） is an orally active inhibitor of p38α MAPK (IC50 <1 μM). When examining BCT197 in vivo, and comparing to vehicle-treated animals, reduced weight loss, improvement in survival and lack of impaired viral control was observed at BCT197 concentrations relevant to those being used in clinical trials of acute exacerbations of chronic obstructive pulmonary disease; at higher concentrations of BCT197 these effects were reduced. BCT197 improved survival and weight loss compared to vehicle, but to a lesser degree than either oseltamivir or dexamethasone. It was also demonstrated that both dexamethasone and the higher dose of BCT197 increased viral load 7 days p.i. The lower dose of BCT197, which is more clinically relevant, remained comparable to vehicle treatment[3]. BCT197 was found to be a low clearance drug (1.76 L/h),with linearity in oral drug clearance (CL/F) demonstrated over the entire dose range tested (0.1–75 mg). No relevant differences in relative bioavailability between these formulations were seen. BCT197 exhibited an apparent absorption plateau, with a tendency to less than dose-proportional increase in peak drug concentration (Cmax)[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.59mL

0.52mL

0.26mL

12.97mL

2.59mL

1.30mL

25.95mL

5.19mL

2.59mL
参考文献

[1]Norman P. Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014 Aug;23(8):1067-77.

[2]X Lin,et al. p38 MAPK: a potential target of chronic pain. Curr Med Chem. 2014;21(38):4405-18.

[3]Growcott E J , Bamba D , Galarneau J . R , et al. The effect of P38 MAP kinase inhibition in a mouse model of influenza[J]. Journal of Medical Microbiology, 2018, 67(3) .

[4]De Buck S , Hueber W , Vitaliti A , et al. Population PK-PD Model for Tolerance Evaluation to the p38 MAP Kinase Inhibitor BCT197[J]. CPT: Pharmacometrics & Systems Pharmacology, 2015, 4(12):691-700.