PDK4-IN-1 hydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PDK4-IN-1 盐酸盐是一种蒽醌衍生物，是丙酮酸脱氢酶激酶 4 的有效口服活性抑制剂（PDK4，IC50 值 = 84 nM）。

PDK4-IN-1 hydrochloride is an anthraquinone derivative and a potent and orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4, IC50 value = 84 nM).(In Vitro):PDK4-IN-1 hydrochloride treatment significantly impedes the proliferation of human colon cancer cell lines, HCT116 and RKO. The colony formation efficiency in HCT116 and RKO cells Is significantly reduced after treatment of PDK4-IN-1 hydrochloride. In HCT116 and RKO cells, PDK4-IN-1 hydrochloride) treatment dose-dependently increased apoptosis. PDK4-IN-1 hydrochloride decreases the expression of BCL-xL and increases the expression of BAX. Cleavage of PARP1 and caspase 3 are increased by PDK4-IN-1 hydrochloride.(In Vivo):PDK4-IN-1 hydrochlorideimproved glucose tolerance in diet-induced obese mice and ameliorated allergic reactions in a passive cutaneous anaphylaxis mouse model. PDK4-IN-1 hydrochloride (C57BL/6J mice) treatment significantly improves glucose tolerance. Pre-incubation with PDK4-IN-1 (compound 8c) dose-dependently inhibits the release of β-hexosaminidase from IgE/antigen-activated BMMCs.

PDK4-IN-1 (Compound 8c; 50 μM; 0-72 hours; HCT116 and RKO cells) treatment significantly impedes the proliferation of human colon cancer cell lines, HCT116 and RKO. The colony formation efficiency in HCT116 and RKO cells Is significantly reduced after treatment of PDK4-IN-1.PDK4-IN-1 (Compound 8c; 10-50 μM; 24 hours; HCT116 and RKO cells) treatment dose-dependently increased apoptosis.PDK4-IN-1 (Compound 8c; 10 μM; 24 hours; HEK293T cells) treatment inhibits phosphorylation of Ser232, Ser293, and Ser300 of PDHE1α.10 μM of PDK4-IN-1 (Compound 8c) significantly increases p-Akt in AML12 cells.PDK4-IN-1 (compound 8c)-induced phosphorylation of p53 on serine 15 is a dose-dependent response in both HCT116 and RKO cells. PDK4-IN-1 decreases the expression of BCL-xL and increases the expression of BAX. Cleavage of PARP1 and caspase 3 are increased by PDK4-IN-1. Cell Viability Assay Cell Line:HCT116 and RKO cells Concentration:50 μM Incubation Time:0 hour, 24 hours, 48 hours, 72hours Result:Significantly impeded the proliferation of human colon cancer cell lines, HCT116 and RKO.Apoptosis Analysis Cell Line:HCT116 and RKO cells Concentration:10 μM, 25 μM, 50 μM Incubation Time:24 hours Result:Dose-dependently increased apoptosis.Western Blot Analysis Cell Line:HEK293T human embryonic kidney cells Concentration: 10 μM Incubation Time:24 hours Result:Inhibited phosphorylation of Ser232, Ser293, and Ser300 of PDHE1α.

PDK4-IN-1 (Compound 8c; 100 mg/kg; oral administration; daily; for 1 week; C57BL/6J mice) treatment significantly improves glucose tolerance.Pre-incubation with PDK4-IN-1 (compound 8c) dose-dependently inhibits the release of β-hexosaminidase from IgE/antigen-activated BMMCs, showing that the absorbance values are 0.26, 0.20, and 0.126 in IgE/Ag, 10 μM, and 20 μM PDK4-IN-1-treated BMMCs.The pharmacokinetic (PK) profiles of PDK4-IN-1 (compound 8c) are evaluated in rat. PDK4-IN-1 shows good bioavailability (64%), long half-life (>7 h), and moderate clearance (CL of 0.69) in rats. Animal Model:C57BL/6J mice (8-week old) fed with high-fat diet Dosage:100 mg/kg Administration:Oral administration; daily; for 1 week Result:Significantly improved glucose tolerance.

——

Apoptosis

Apoptosis

5-HT2| D2| D3| D4| Sigma receptor| α-adrenergic receptor

——

——

2310262-11-2

393.87

C22H20ClN3O2

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (317.36 mM)

Cl.O=C1c2ccccc2C(=O)c2c(cccc12)-c1cnn(c1)C1CCNCC1

——

(-20℃)

With Ice Pack

≥ 2 years