CHIR-99021

GSK-3α,10 nM (cell free)

GSK-3β,6.7 nM (cell free)

浣撳鐮旂┒

CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases. Furthermore, CHIR-99021 shows only weak binding to a panel of 22 pharmacologically relevant receptors and little inhibitory activity against a panel of 23 nonkinase enzymes. CHIR-99021 induces the activation of glycogen synthase (GS) in insulin receptor-expressing CHO-IR cells with EC50 of 0.763 μM[1].

浣撳唴鐮旂┒

Oral administration of CHIR-99021 at 30 mg/kg enhances glucose metabolism in a rodent model of type 2 diabetes, with a maximal plasma glucose reduction of nearly 150 mg/dl 3-4 hours after administration, while plasma insulin remains at or below control levels. Oral administration of CHIR-99021 at 16 or 48 mg/kg 1 hour before oral glucose challenges in ZDF rats significantly improves glucose tolerance with 14% and 33% reduction in plasma glucose at 16 mg/kg and 48 mg/kg, respectively, and the higher dose of CHIR-99021 also reduces hyperglycemia before the oral glucose challenge[1].

缁嗚優瀹為獙

Cell lines: Insulin receptor鈥揺xpressing CHO-IR cells; Primary rat hepatocytes

Concentrations: 0.01-10 μM

Incubation Time: 30 min

Method:CHO-IR cells expressing human insulin receptor are grown to 80% confluence in Hamm鈥檚 F12 medium with 10% fetal bovine serum and without hypoxanthine. Trypsinized cells are seeded in 6-well plates at 1 × 106 cells/well in 2 ml of medium without fetal bovine serum. After 24 h, medium is replaced with 1 ml of serum-free medium containing GSK-3 inhibitor or control (final DMSO concentration <0.1%) for 30 min at 37°C. Cells are lysed and centrifuged 15 min at 4°C/14000g. The activity ratio of GS is calculated as the GS activity in the absence of glucose-6-phosphate divided by the activity in the presence of 5 mmol/l glucose-6-phosphate, using the filter paper assay of Thomas et al.

(Only for Reference)

鍔ㄧ墿瀹為獙

Animal Models: Female db/db mice; Male ZDF rats

Formulation: HCl salts formulated

Dosages: 8-48 mg/kg

Administration: oral administration

(Only for Reference)

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[1] Ring DB, et al. Diabetes. 2003, 52(3):588-595.

瀹夊叏淇℃伅

鍥惧舰鎴栧嵄瀹虫爣蹇桙/td>
鎻愮ず璇?/td>	Danger
鍗遍櫓璇存槑	H300 H315 H319 H335
闃茶寖璇存槑	P261 P264 P301+P310 P305+P351+P338
UN鍙风爜	2811
鍗遍櫓鍒嗙被	6.1
鍖呰绛夌骇	III