| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Animal experiment: | Rats: BAY 85-3934 is prepared as a solution in ethanol:Solutol HS 15:water (10:20:70). In a repeat-dose, 26-day experiment, male Wistar rats (240–340 g in body weight) are administered vehicle or BAY 85-3934 at doses of 0.5 mg/kg, 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg. The efficacy of BAY 85-3934 (2.5 mg/kg, once-daily, oral) is also compared with that of rhEPO (25 IU/kg, 50 IU/kg, and 100 IU/kg, twice-weekly, s.c. injection). The time-course of induction of EPO mRNA expression and plasma EPO is determined at baseline and 0.5 h, 1 h, 2 h, 4 h, 6 h, and 8 h after oral administration of a single dose of BAY 85-3934 (5 mg/kg)[1]. Monkey: BAY 85-3934 is prepared as a solution in 0.5% tylose. Male and female cynomolgus monkeys (2.8–5.6 kg in body weight) are administered at doses of 0.5 mg/kg and 1.5 mg/kg at 0 h, 24 h, 48 h, 72 h, and 96 h. Blood samples are taken at 7 h, 31 h, 55 h, 79 h, 103 h, and 168 h. Erythropoietic parameters are also evaluated after a 2-week treatment period with s.c. administration of rhEPO (100 IU/kg twice weekly at days 1, 4, 8, and 11) and BAY 85-3934 (1.5 mg/kg) once daily[1]. |
| 产品描述 | Molidustat (BAY85-3934) Description: IC50: 480 nM, 280 nM, and 450 nM for PHD1, PHD2, and PHD3, respectively. Oxygen sensing via hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) is the dominant regulatory mechanism of erythropoietin (EPO) expression. In chronic kidney disease (CKD), impaired EPO expression causes anemia, which can be treated by supplementation with recombinant human EPO (rhEPO). Molidustat (BAY85-3934) is a novel HIF-PH inhibitor. In vitro: The IC50 values were found to be dependent on the 2-oxoglutarate concentration in the reaction buffer. By lowering the 2-oxoglutarate concentration from 20 μM to 0.3 μM, the potency of the test compound increased up to 10-fold. Variation of the concentrations of Fe2+ and ascorbate in the reaction buffer by factors of 30 and 200, respectively, did not alter the potency of the inhibitor by more than 2-fold [1]. In vivo: In repeat dosing of BAY 85-3934, hemoglobin levels were increased compared with animals in vehicle group, while endogenous EPO remained within the normal physiological range. BAY 85-3934 therapy was also effective in the treatment of renal anemia in rats with impaired kidney function and, unlike treatment with rhEPO, resulted in normalization of hypertensive blood pressure in a rat model of CKD [1]. Clinical trial: Clinical studies are still ongoing to investigate the effects of BAY 85-3934 therapy in patients with renal anemia (https://clinicaltrials.gov/ct2/show/NCT01332942?term=Molidustat&rank=2). Reference: |
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