Molidustat
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 525715

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.


Chemical Structure

img
Molidustat
CAS# 1154028-82-6

Theoretical Analysis

MedKoo Cat#: 525715
Name: Molidustat
CAS#: 1154028-82-6
Chemical Formula: C13H14N8O2
Exact Mass: 314.12397
Molecular Weight: 314.3
Elemental Analysis: C, 49.68; H, 4.49; N, 35.65; O, 10.18

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Same Day
50.0mg USD 250.0 Same Day
100.0mg USD 450.0 Same Day
200.0mg USD 650.0 Same Day
500.0mg USD 1250.0 Same Day
1.0g USD 2150.0 Same Day
2.0g USD 3650.0 Same Day
5.0g USD 5450.0 Same Day
Click to view more sizes and prices
Bulk inquiry

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

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 5.0 15.91
5% TFA 1.67 5.31

Preparing Stock Solutions

The following data is based on the product molecular weight 314.3 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.

Recalculate based on batch purity %
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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x



Additional Information