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PDK4-IN-1 HCl

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Chemical Structure| 2310262-11-2 同义名 : PDK4-IN-1 hydrochloride
CAS号 : 2310262-11-2
货号 : A1258083
分子式 : C22H20ClN3O2
纯度 : 99%+
分子量 : 393.866
MDL号 : N/A
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(266.59 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Among the four isotypes (PDK1-4), Pyruvate dehydrogenase kinase 4 (PDK4) is mainly and drastically increased in the liver, skeletal muscle, and adipose tissue. Its activation is associated with metabolic diseases including hyperglycemia, insulin resistance, allergies, and cancer. PDK4-IN-1 hydrochloride, an anthraquinone derivative, is a potent and orally active allosteric PDK4 inhibitor with an IC50 value of 84 nM. In HEK293T human embryonic kidney cells, PDK4-IN-1 hydrochloride (10 μM) successfully inhibited phosphorylation of Ser232, Ser293, and Ser300 of PDHE1α. PDK4-IN-1 hydrochloride showed good bioavailability (64%), long half-life (>7 h), and moderate clearance (CL = 0.69) in rats. Diet-induced obese mice were orally treated with 100 mg of PDK4-IN-1 hydrochloride for 1 week, and it significantly improved glucose tolerance, as quantified by the area under the curve (AUC). Pre-incubation with PDK4-IN-1 dose-dependently inhibited the release of β-hexosaminidase from IgE/antigen-activated BMMCs, showing that the absorbance values are 0.26 ± 0.025, 0.20 ± 0.015, and 0.126 ± 0.032 in IgE/Ag, 10 μM, and 20 μM PDK4-IN-1-treated BMMCs. PDK4-treated mice showed a marked reduction in extravasation by Evans blue solution. Levels of Evans blue exudation was 149.0 ± 16.9, and 49.9 ± 24.1 in vehicle, and 50 mg/kg PDK4-IN-1-treated mice. In addition, CCK-8 assay showed that the treatment of 50 μM compound PDK4-IN-1 hydrochloride significantly impeded the proliferation of human colon cancer cell lines, HCT116 and RKO[1].
作用机制 The predicted PDK4/inhibitor complex displayed an optimal fitting of the compound into the lipoamide binding site[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.54mL

0.51mL

0.25mL

12.69mL

2.54mL

1.27mL

25.39mL

5.08mL

2.54mL
参考文献

[1]Lee D, Pagire HS, Pagire SH, et al. Discovery of Novel Pyruvate Dehydrogenase Kinase 4 Inhibitors for Potential Oral Treatment of Metabolic Diseases [published correction appears in J Med Chem. 2019 Mar 14;62(5):2849]. J Med Chem. 2019;62(2):575‐588