WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H525715
CAS#: 1154028-82-6
Description: Molidustat, also known as BAY 85-3934, is a novel inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) which stimulates erythropoietin (EPO) production and the formation of red blood cells. Phase I data have shown that inhibition of HIF-PH by Molidustat results in an increase in endogenous production of EPO. Molidustat is currently clinical trials at Bayer for the treatment of patients suffering from renal anemia due to chronic kidney disease.
Hodoodo Cat#: H525715
Name: Molidustat
CAS#: 1154028-82-6
Chemical Formula: C13H14N8O2
Exact Mass: 314.12
Molecular Weight: 314.300
Elemental Analysis: C, 49.68; H, 4.49; N, 35.65; O, 10.18
Related CAS #: 1154025-82-6
Synonym: BAY 85-3934; BAY-85-3934; BAY85-3934; BAY 853934; BAY-853934; BAY853934; Molidustat.
IUPAC/Chemical Name: 2-(6-morpholinopyrimidin-4-yl)-4-(1H-1,2,3-triazol-1-yl)-1H-pyrazol-3(2H)-one
InChi Key: IJMBOKOTALXLKS-UHFFFAOYSA-N
InChi Code: InChI=1S/C13H14N8O2/c22-13-10(20-2-1-16-18-20)8-17-21(13)12-7-11(14-9-15-12)19-3-5-23-6-4-19/h1-2,7-9,17H,3-6H2
SMILES Code: O=C1N(C2=NC=NC(N3CCOCC3)=C2)NC=C1N4N=NC=C4
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, DMF, and 1:1 DMF:PBS
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Stabilizes HIF-1α and inhibits prolyl hydroxylase. |
| In vitro activity: | Using this cell model Molidustat was observed to stabilize HIF-1α in the case of the highest (50 μM) concentration of the compound (Fig. 1A), however, the expression of VEGF, a known HIF-1-dependent gene, was increased already by 10 µM molidustat after 24 h treatment. Both VEGF mRNA expression and protein release to the media were increased after 24 h and 48 h (Fig. 1 B, C). his compound enhanced VEGF expression to a similar or even higher level as hypoxia (Fig. 1 B, C). At the highest dose (50 μM), a nearly two-fold decrease in cell survival was observed after 72 h as compared to 48 h (Fig. 2A). Additionally, the clonogenic potential of MDA-MB-231 cells in response to molidustat was tested. The ability of cells to form colonies was slightly impaired after 10 μM molidustat (Fig. 2B). However, the number of colonies was greatly diminished in the wells with 25 μM inhibitor added. At the highest concentration, cell survival was dramatically affected to the level, where no colonies could be observed. To check whether molidustat induces cell apoptosis, flow cytometry analysis using double staining with Hoechst/7-AAD was performed. There was an increase in the apoptotic fraction after 72 h of the treatment only at the highest inhibitor concentration in comparison to untreated cells (Fig. 2C). However, the percentage of apoptotic cells was rather small (up to 8%) pointing at other pathways implemented in the decreased breast cancer cell viability. Reference: Biochem Pharmacol. 2020 May;175:113922. https://www.sciencedirect.com/science/article/pii/S0006295220301507?via%3Dihub |
| In vivo activity: | HIF stabilization by oral administration of the HIF-PH inhibitor BAY 85-3934 (molidustat) results in dose-dependent production of EPO in healthy Wistar rats and cynomolgus monkeys. Molidustat therapy is aldo 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 Reference: PLoS One. 2014 Nov 13;9(11):e111838. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230943/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.0 | 15.91 | |
| 5% TFA | 1.7 | 5.31 |
The following data is based on the product molecular weight 314.30 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Kachamakova-Trojanowska N, Podkalicka P, Bogacz T, Barwacz S, Józkowicz A, Dulak J, Łoboda A. HIF-1 stabilization exerts anticancer effects in breast cancer cells in vitro and in vivo. Biochem Pharmacol. 2020 May;175:113922. doi: 10.1016/j.bcp.2020.113922. Epub 2020 Mar 20. PMID: 32205093. 2. Coyle RC, Barrs RW, Richards DJ, Ladd EP, Menick DR, Mei Y. Targeting HIF-α for robust prevascularization of human cardiac organoids. J Tissue Eng Regen Med. 2021 Feb;15(2):189-202. doi: 10.1002/term.3165. Epub 2020 Dec 8. PMID: 33868541; PMCID: PMC8049092. 3. 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. doi: 10.1371/journal.pone.0111838. PMID: 25392999; PMCID: PMC4230943. 4. Zhang A, Nakano D, Morisawa N, Kitada K, Kittikulsuth W, Rahman A, Morikawa T, Konishi Y, Nishiyama A. Effects of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, on sodium dynamics in hypertensive subtotally nephrectomized rats. J Pharmacol Sci. 2021 Jun;146(2):98-104. doi: 10.1016/j.jphs.2021.03.007. Epub 2021 Mar 31. PMID: 33941326. |
| In vitro protocol: | 1. Kachamakova-Trojanowska N, Podkalicka P, Bogacz T, Barwacz S, Józkowicz A, Dulak J, Łoboda A. HIF-1 stabilization exerts anticancer effects in breast cancer cells in vitro and in vivo. Biochem Pharmacol. 2020 May;175:113922. doi: 10.1016/j.bcp.2020.113922. Epub 2020 Mar 20. PMID: 32205093. 2. Coyle RC, Barrs RW, Richards DJ, Ladd EP, Menick DR, Mei Y. Targeting HIF-α for robust prevascularization of human cardiac organoids. J Tissue Eng Regen Med. 2021 Feb;15(2):189-202. doi: 10.1002/term.3165. Epub 2020 Dec 8. PMID: 33868541; PMCID: PMC8049092. |
| In vivo protocol: | 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. doi: 10.1371/journal.pone.0111838. PMID: 25392999; PMCID: PMC4230943. 2. Zhang A, Nakano D, Morisawa N, Kitada K, Kittikulsuth W, Rahman A, Morikawa T, Konishi Y, Nishiyama A. Effects of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, on sodium dynamics in hypertensive subtotally nephrectomized rats. J Pharmacol Sci. 2021 Jun;146(2):98-104. doi: 10.1016/j.jphs.2021.03.007. Epub 2021 Mar 31. PMID: 33941326. |
