Mizagliflozin

Mizagliflozin, a novel SGLT1 inhibitor with a Ki value of 27.0±1.5nM, can be used to treat diabetes and modify postprandial blood glucose excursion^[1].

Mizagliflozin was administrated to Renal cyst lining epithelial cells OX161 and renal tubular epithelial cells UCL93, incubated at 37℃ for 24, 48, and 72h, and found that Mizagliflozin inhibited the proliferation and fibrosis of polycystic kidney cells in a concentration and time dependent manner^[2]. Mizagliflozin, 1μM or 10μM added to Rat PC12HS cells to pretreat for 24h or posttreat for 6h, ameliorated IL-1β-induced decreases in the survival rate of PC12HS cells, and regardless of the administration start time^[3].

Mizagliflozin given to diabetic mice at a low dose (0.5mg/kg) or a high dose (1.0mg/kg) via stomach gavage for 8 weeks, and mesangial cells were isolated and subjected to high glucose conditions in culture to assess the effects of Mizagliflozin on diabetic nephropathy. The results showed that low doses of Mizagliflozin significantly reduced albuminuria to a level comparable to that achieved with high doses in db/db mice. High doses of Mizagliflozin led to a substantial increase in body weight in mice, along with decreased blood glucose levels and food intake^[4]. Mizagliflozin administrated intravenously (0.3mg/kg) and orally (3mg/kg) in rats declined with a short half-life (0.23 and 1.14h, respectively), the absolute bioavailability was only 0.02%. Up to 24h after oral administration of [14C]Mizagliflozin (1mg/kg), radioactivity was recovered in the faeces (98.4%) and in the urine (0.8%)^[5].

References:
[1] Inoue Toshihiro,Takemura Masaaki,Fushimi Nobuhiko et al. Mizagliflozin, a novel selective SGLT1 inhibitor, exhibits potential in the amelioration of chronic constipation.[J] .Eur J Pharmacol, 2017, 806: 25-31.
[2] Liu W, Shuangcheng W U, Zhang T, et al. Mizagliflozin inhibits proliferation and fibrosis of autosomal dominant polycystic kidney cells by inhibiting function of sodium-glucose cotransporter 1[J]. Academic Journal of Naval Medical University, 2024, 45(11): 1343-1351.
[3] Ishida N, Saito M, Sato S, et al. Mizagliflozin, a selective SGLT1 inhibitor, improves vascular cognitive impairment in a mouse model of small vessel disease[J]. Pharmacology Research & Perspectives, 2021, 9(5): e00869.
[4] Lin Z M, Gao H Y, Shi S H, et al. Mizagliflozin ameliorates diabetes induced kidney injury by inhibitor inhibit inflammation and oxidative stress[J]. World Journal of Diabetes, 2025, 16(1): 92711.
[5] Ohno H, Kojima Y, Harada H, et al. Absorption, disposition, metabolism and excretion of [14C] mizagliflozin, a novel selective SGLT1 inhibitor, in rats[J]. Xenobiotica, 2019, 49(4): 463-473.

Mizagliflozin是一种新型的SGLT1抑制剂，抑制常数Ki为27.0±1.5nM，可用于治疗糖尿病，改善餐后血糖波动^[1]。

Mizagliflozin作用于肾囊肿衬里上皮细胞OX161和肾小管上皮细胞UCL93，在 37℃下孵育24h、48h和 72h，结果发现Mizagliflozin以浓度和时间依赖的方式抑制多囊肾细胞的增殖和纤维化^[2]。使用1μM或10μM Mizagliflozin在IL-1β应用前24h或应用后6h处理大鼠PC12HS细胞，均可改善IL-1β诱导的PC12HS细胞存活率下降的情况，且与给药起始时间无关^[3]。

给糖尿病小鼠分别以低剂量（0.5mg/kg）或高剂量（1.0mg/kg）的Mizagliflozin进行为期8周的灌胃后，分离系膜细胞并培养于高糖条件下，评估Mizagliflozin对糖尿病肾病的影响。结果表明，低剂量的Mizagliflozin可显著降低 db/db 小鼠的蛋白尿水平，效果与高剂量相当。高剂量的Mizagliflozin会使小鼠体重显著增加，同时血糖水平和食物摄入量下降^[4]。给大鼠静脉注射（0.3mg/kg）和口服（3mg/kg）Mizagliflozin后，其在体内的消除半衰期较短（分别为0.23h和1.14h），绝对生物利用度仅为0.02%。口服[14C]Mizagliflozin（1mg/kg）后24h内，粪便中放射性回收率为98.4%，尿液中为0.8%^[5]。