Anagliptin (SK-0403) hydrochloride 是一种高选择性的、有效的、具有口服活性的二肽酰肽酶 4 (DPP-4) 抑制剂，IC50值为 3.8 nM，对DPP-8和DDP-9的选择性相对较弱，IC50值分别为 68 nM 和 60 nM。

Anagliptin (SK-0403) hydrochloride is a highly selective, potent, orally active inhibitor of dipeptidyl peptidase 4 (DPP-4), with an IC 50 of 3.8 nM, and less selective at DPP-8 and DDP-9 with IC 50 s of 68 nM and 60 nM, respectively [1].

Anagliptin (SK-0403) (0-100 μM; 24 h) attenuates s-DPP-4-induced smooth muscle cells proliferation [2]. Anagliptin (100 μM; 10 min) reduces TNF-α production in cultured monocytes [2]. Anagliptin (0.001-10 μM; 24 h) significantly suppresses sterol regulatory element‐inding protein activity in HepG2 cells (21% decrease) [3]. Cell Proliferation Assay [2] Cell Line: Rat smooth muscle cells (SMC) Concentration: 1, 10 and 100 μM Incubation Time: 24 h Result: Attenuated s-DPP-4-induced SMC proliferation in a dose-dependent manner. Inhibited LPS-induced ERK phosphorylation and markedly suppressed LPS-induced nuclear translocation of NF-κBp65. Western Blot Analysis [2] Cell Line: Rat smooth muscle cells (SMC) Concentration: 100 μM Incubation Time: 10 min Result: Blocked the early- but not the late-phase ERK phosphorylation induced by s-DPP-4.

Anagliptin (SK-0403) (0.3%; in diet; 16 weeks) reduces atherosclerotic lesion and does not increase the number of circulating EPCs in apoliporotein E (apoE)-deficient mice [2]. Anagliptin (0.3%; in diet; 4 weeks) exhibits a lipid‐lowering effect in a hyperlipidemic mice model [3]. Animal Model: Male apoliporotein E (apoE)-deficient mice [2] Dosage: 0.3% Administration: In diet, 16 weeks Result: Reduced DPP-4 activity in the plasma as expected and did not affect food consumption or body weight gain. Significantly reduced total cholesterol level, especially VLDL and LDL-C without affecting triglyceride level. Also decreased the α-SMA-positive area within the individual plaque. Animal Model: Male low‐density lipoprotein receptor‐deficient mice (B6.129S7‐Ldlr tm1Her /J) [3] Dosage: 0.3% Administration: In diet, 4 weeks Result: Significantly decreased the plasma total cholesterol (14% reduction) and triglyceride levels (27% reduction). Significantly decreased low‐density lipoprotein cholesterol and very low‐density lipoprotein cholesterol. Sterol regulatory element‐inding protein‐2 messenger ribonucleic acid expression level was significantly decreased at night. Animal Model: Male Sprague–Dawley rats and Beagle dogs [1] Dosage: 0.2, 0.5, 1 and 10 mg/kg Administration: Oral or intravenous administration (Pharmacokinetic Studies) Result: Selected PK parameters of Anagliptin hydrochloride in rats and dogs [1] Compound Species CL tot (l/h/kg) V dss (l/h/kg) C max c (ng/ml) T max c (h) T 1/2 (h) AUC (ng/h/ml) BA (%) Anagliptin hydrochloride a Rat 2.00 (iv) 0.68 (iv) 309 (62) (po) 0.8 (2.3) (po) 1.9 (po) 1160 (po) 23 (po) Dog 0.65 (iv) 0.83 (iv) 261 (po) 1.5 (po) 1.0 (po) 824 (po) 100 (po) a Anagliptin hydrochloride dose in rats, 1 mg/kg, iv (n = 3); 10 mg/kg, po (n = 3). 4a dose in dogs, 0.2 mg/kg, iv (n = 3); 0.5 mg/kg, po (n = 2). c Values in parentheses were obtained at a dose of 3 mg/kg (n = 3).

1359670-56-6

C19H26ClN7O2

419.91

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years