Molidustat (BAY85-3934) (Synonyms: Molidustat) |
| Catalog No.GC10046 |
Molidustat (BAY85-3934) (BAY 85-3934) is a novel inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) with mean IC50 values of 480 nM for PHD1, 280 nM for PHD2, and 450 nM for PHD3.
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Cas No.: 1154028-82-6
Sample solution is provided at 25 µL, 10mM.
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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:
[1] Flamme I, Oehme F, Ellinghaus P, Jeske M, Keldenich J, Thuss U. Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat) stimulates erythropoietin production without hypertensive effects. PLoS One. 2014 Nov 13;9(11):e111838.
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]. |
References: [1]. Flamme I, et al. Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat) stimulates erythropoietin production without hypertensive effects. PLoS One. 2014 Nov 13;9(11):e111838. | |
| Cas No. | 1154028-82-6 | SDF | |
| Synonyms | Molidustat | ||
| Chemical Name | 2-(6-morpholinopyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-3(2H)-one | ||
| Canonical SMILES | O=C1C(N2C=CN=N2)=CNN1C3=NC=NC(N4CCOCC4)=C3 | ||
| Formula | C13H14N8O2 | M.Wt | 314.3 |
| Solubility | ≥ 5.68mg/mL in DMF | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.1817 mL | 15.9084 mL | 31.8167 mL |
| 5 mM | 0.6363 mL | 3.1817 mL | 6.3633 mL |
| 10 mM | 0.3182 mL | 1.5908 mL | 3.1817 mL |
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Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)
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