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Molidustat

Manufactured by Selleck Chemicals
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Sourced in United States

Molidustat is a laboratory equipment product designed for use in chemical and biological research. It functions as a hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, which helps regulate cellular responses to changes in oxygen levels. The core function of Molidustat is to modulate HIF activity, but no further interpretation or extrapolation on its intended use is provided.

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Lab products found in correlation

Rpmi 1640, by Thermo Fisher Scientific (1 mentions) Glutamine, by Merck Group (1 mentions) Atcc 27294, by American Type Culture Collection (1 mentions) Human ab serum, by Merck Group (1 mentions) Penicillin, by Harvard Bioscience (1 mentions) Streptomycin, by Harvard Bioscience (1 mentions) Puromycin, by Merck Group (1 mentions) Bay 87 2243, by Selleck Chemicals (1 mentions) Roxadustat, by Selleck Chemicals (1 mentions) Daprodustat, by MedChemExpress (1 mentions) Gsk j4, by Bio-Techne (1 mentions) Succinate, by Merck Group (1 mentions) Dimethyl fumarate, by Merck Group (1 mentions) Panobinostat, by Cayman Chemical (1 mentions) Roxadustat, by Cayman Chemical (1 mentions) Gsk j1, by Bio-Techne (1 mentions) Jib 04, by Bio-Techne (1 mentions) Qc6352, by MedChemExpress (1 mentions) Dimethyl 2 oxoglutarate, by Merck Group (1 mentions) Dimethyl succinate, by Merck Group (1 mentions)

6 protocols using molidustat

1

Mycobacterial antigen extraction and THP-1 cell culture

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Primary human cells were cultured in RPMI 1640 (Life Technologies) supplemented with 2 mM glutamine (Sigma), 10 mM HEPES, 13 mM NaHCO3, 100 µg/ml streptomycin, 60 µg/ml penicillin (all from Biochrom) and 5% heat-inactivated human AB serum (Sigma) (complete medium). For THP-1 cells (ATCC® TIB-202™, Institute for Medical Microbiology and Hygiene, Ulm University) heat-inactivated human AB serum was replaced by 20% fetal calf serum ([FCS] Sigma). For experiments involving the virulent laboratory strain Mtb H37Rv (ATCC® 27294™, Institute for Medical Microbiology and Hygiene, Ulm University) the medium was modified to optimize phagocytosis (non-heat-inactivated serum) and allow multiplication of the bacteria (no streptomycin). In order to prevent fungal growth 5.6 µg/ml Amphotericin B and 60 µg/ml penicillin G were added. Mtb-extract was used as source for soluble mycobacterial antigens in a final concentration of 10 µg/ml. These antigens were generated by collecting the ultracentrifuged supernatant of mycobacterial cells that were repeatedly sonicated. Afterwards cell wall components and intracellular antigens were extracted (24 ). Molidustat (BAY 85-3934, Selleckchem) is a HIF-stabilizer (prolyl-hydroxylase inhibitor), which was dissolved in DMSO and serially diluted in PBS.
Zenk S.F., Hauck S., Mayer D., Grieshober M, & Stenger S. (2021). Stabilization of Hypoxia-Inducible Factor Promotes Antimicrobial Activity of Human Macrophages Against Mycobacterium tuberculosis. Frontiers in Immunology, 12, 678354.
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2

HIF-1α Modulation in Lung Cells

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Human normal lung epithelial cell line HFL-1, and lung cancer cell lines 95D, A549, PC-9, SPC-A1 and HAC-84 were purchased from Chinese Academy of Science. HFL-1 cells were cultured in F-12K medium containing 10% fetal bovine serum (FBS), other cell lines were maintained in RMPI-1640 medium supplemented with 10% FBS. All cells were incubated at 37°C with 5% CO2.
Molidustat (10 μM; Selleck, China) was used to treat cells for 4h to mimic HIF-1α activation. BAY87-2243 (10 μM; Selleck, China) was used to treat cells for 48h to induce HIF-1 inhibition. Proteasome inhibitor MG132 (25 μM; MedChem Express, China) and protein translation inhibitor puromycin (2 μM; Sigma, USA) were also used to treat cells for indicated time. Then cells were harvested for Western blot or real-time PCR.
Jin Y., Xie H., Duan L., Zhao D., Ding J, & Jiang G. (2019). Long Non-Coding RNA CASC9 And HIF-1α Form A Positive Feedback Loop To Facilitate Cell Proliferation And Metastasis In Lung Cancer. OncoTargets and therapy, 12, 9017-9027.
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3

Molidustat Restores RBC Indices in Mice

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After 12 weeks of experimental diets, mice received intraperitoneal (i.p.) injections of either vehicle (5% DMSO + 45% PEG300 + 50% ddH2O) or BAY 85–3934 (BAY, Molidustat; SelleckChem [Houston, TX, USA] S8138 resuspended in vehicle) at a human equivalent dose for mice(28 (link)) of 20 mg/kg every other day for 3 weeks. Final red blood cell indices were measured the day of tissue harvest; tissues were harvested 4 hours after the final injection at the end of the 3-week treatment window (15 weeks from experimental diet initiation).
Noonan M.L., Ni P., Agoro R., Sacks S.A., Swallow E.A., Wheeler J.A., Clinkenbeard E.L., Capitano M.L., Prideaux M., Atkins G.J., Thompson W.R., Allen M.R., Broxmeyer H.E, & White K.E. (2021). The HIF-PHI BAY 85–3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 36(6), 1117-1130.
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4

Investigating FGF23 regulation in mice

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8-week-old wild type female mice received intraperitoneal (i.p.) injections of either vehicle (5%DMSO/45%PEG300/50%ddH2O) or 50 mg·kg−1 of FG-4592 (‘FG’, Roxadustat; SelleckChem) or BAY 85-3934 (‘BAY’, Molidustat; SelleckChem) every other day for 5 days (3 injections total). Female flox-Fgf23/Dmp1-cre+ and cre− mice (10-11 weeks old) were injected with 70 mg·kg−1 of FG-4592 every other day for 5 days (3 injections total). In all studies, tissues were harvested 4 hours after the final injection.
Noonan M.L., Ni P., Solis E., Marambio Y.G., Agoro R., Chu X., Wang Y., Gao H., Xuei X., Clinkenbeard E.L., Jiang G., Liu S., Stegen S., Carmeliet G., Thompson W.R., Liu Y., Wan J, & White K.E. (2023). Osteocyte Egln1/Phd2 links oxygen sensing and biomineralization via FGF23. Bone Research, 11, 7.
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5

Comprehensive Compound Sourcing for Metabolic Research

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IOX1,
IOX2, ML324, KDMOAM25, succinate,
fumarate, 2OG, dimethylpyridine-2,4-dicarboxylate, dimethyl 2-oxoglutarate,
dimethyl succinate, dimethyl fumarate, and DMOG were purchased from
Sigma-Aldrich, while IOX3, IOX4, Roxadustat, Vadadustat, Panobinostat,
disodium 2S/2R-hydroxyglutarate, and FG0041 were
obtained from Cayman Chemical Company. 2,4-PDCA (Alfa Aesar), Daprodustat
(MedChemExpress), QC6352 (MedChemExpress), Molidustat (Selleck Chem),
JIB-04 (Tocris Bioscience), GSK-J1 (Tocris Bioscience), GSK-J4 (Tocris
Bioscience), SD70 (Xcess Biosciences), CPI455 (Axon Med Chem), 2′-deoxy-5-methylcytidine
(TCI Chemicals), 2′-deoxy-5-(hydroxymethyl)cytidine (TCI Chemicals),
and (R/S)-Octyl-α-hydroxyglutarate
(Cambridge Bioscience) were purchased from other commercial sources.
All purchased inhibitors were >95% pure as determined by the manufacturer.
Key compound purity was verified using analytical HPLC using a UV
detector (210 or 254 nm) or CAD detector (Figures S18–S28). NOG was synthesized as described in the materials
and methods and has a purity >95% as determined by HPLC. All buffer
components were from Sigma-Aldrich unless otherwise stated.
Belle R., Saraç H., Salah E., Bhushan B., Szykowska A., Roper G., Tumber A., Kriaucionis S., Burgess-Brown N., Schofield C.J., Brown T, & Kawamura A. (2024). Focused Screening Identifies Different Sensitivities of Human TET Oxygenases to the Oncometabolite 2-Hydroxyglutarate. Journal of Medicinal Chemistry, 67(6), 4525-4540.
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6

Stabilizing HIF-1α with Pharmacological Agents

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HIF-1α was stabilized with a variety of drugs: Deferoxamine (DFO, MilliporeSigma, Burlington, MA, USA); Deferasirox (DFX, ChemScene, Monmouth Junction, NJ, USA for in vitro studies, and Novartis, Basel, Switzerland for in vivo studies); BAY 85-3934 (Molidustat, Selleck Chemicals, Houston, TX, USA); and MLN-4924 (Pevonedistat, Adooq Bioscience, Irvine, CA, USA, #A11260). DFO and gemcitabine (Gem, MilliporeSigma) stock solutions were prepared in PBS for in vitro and in vivo studies. DFX, BAY-3934, and MLN-4924 stock solutions were prepared in DMSO for in vitro studies. DFX was prepared in 30% 1,2-propanediol/70% sterile 0.9% sodium chloride solution (v/v) for oral gavage treatment. Ganciclovir (MilliporeSigma) stock solutions were prepared in 0.1 M HCl.
Cordes B.L., Bilger A., Kraus R.J., Ward-Shaw E.T., Labott M.R., Lee S., Lambert P.F, & Mertz J.E. (2023). Drugs That Mimic Hypoxia Selectively Target EBV-Positive Gastric Cancer Cells. Cancers, 15(6), 1846.
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