Delving into the Latest Updates on Molidustat Sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BAY1053048（ナトリウム塩）, BAY85-3934（遊離塩基）, Molidustat

+ [8]

Target

HIF-PHs

Action

inhibitors

Mechanism

HIF-PHs inhibitors(Hypoxia-inducible factor prolyl hydroxylase inhibitors)

Therapeutic Areas

Hemic and Lymphatic DiseasesUrogenital Diseases

Active Indication

Anemia in chronic kidney disease

Inactive Indication

Anemia of renal disease

Originator Organization

Bayer AG

Active Organization

Bayer AG

Inactive Organization

Bayer HealthCare AGBayer Schering Pharma AG

License Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (22 Jan 2021),

Anemia in chronic kidney disease

RegulationSpecial Review Project (China)

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Structure/Sequence

Molecular FormulaC13H14N8NaO2

InChIKeyHCTDSMITRFYAKD-UHFFFAOYSA-N

CAS Registry1375799-59-9

In this study, the researchers want to learn more about the safety and effectiveness of Molidustat in Japanese men and women who have renal anemia, a condition in which the kidneys do not make enough of a hormone that helps the body make new red blood cells.
In previous clinical trials with a small number of participants, several important adverse events were observed. The researchers in this study want to know how many patients also have these adverse events under the real world, and if the number of the red blood cells will be increased after the treatment of Molidustat.
The researchers will collect the participants' health information from their medical records and their regular check-ups for up to 2 years. The data from this study will be submitted to the health authority in Japan in accordance with the local regulation.

Start Date06 Aug 2021

Sponsor / Collaborator

Bayer AG

NCT03543657

/ CompletedPhase 3

A Randomized, Active-controlled, Double-blinded, Double-dummy, Parallel-group, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Comparison to Darbepoetin Alfa in Dialysis Subjects Treated With Erythropoiesis-Stimulating Agents (ESAs)

The purpose of this study is to evaluate the efficacy and safety of molidustat in comparison to darbepoetin alfa in dialysis subjects with renal anemia who are treated with Erythropoiesis-Stimulating Agents (ESAs).

Start Date23 Jun 2018

Sponsor / Collaborator

Bayer AG

100 Clinical Results associated with Molidustat Sodium

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100 Translational Medicine associated with Molidustat Sodium

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100 Patents (Medical) associated with Molidustat Sodium

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91

Literatures (Medical) associated with Molidustat Sodium

01 May 2025·Drug Testing and Analysis

Simultaneous detection of three hypoxia‐inducible factor stabilizers—molidustat, roxadustat, and vadadustat—in multiple keratinized matrices and its application in a doping context

Article

Author: Kintz, Pascal ; Arbouche, Nadia ; Gheddar, Laurie ; Raul, Jean‐Sébastien ; Checkouri, Anne

AbstractIn a doping case, a top athlete challenged an anti‐doping rule violation, involving molidustat. Molidustat is a stabilizing agent of the hypoxia‐inducible factor (HIF) recently developed. It is currently undergoing clinical trials for anemia associated with chronic kidney disease. HIF stabilizers are banned at all times by the World Anti‐Doping Agency (class S2). Because of their pharmacological proprieties, these new drugs can enhance athletic performance. The athlete's defense wanted to analyze multiple keratinized matrices as they allow long‐term investigations. Requests concerning HIF stabilizers are constantly growing. We have therefore developed a liquid chromatography coupled with tandem mass spectrometry method to identify and quantify three molecules of this class: molidustat, vadadustat, and roxadustat. Thirty milligrams of keratinized matrices were incubated in 1 mL of pH 8.4 diammonium hydrogen phosphate buffer for 16 h at 40°C with 1 ng of testosterone‐D3, used as internal standard. After extraction with ethyl acetate/diethyl ether (80/20), the organic phase was evaporated, and the dry residue was reconstituted in 30 μL of initial phase. The method was linear from 5 to 1000 pg/mg for the three analytes. Limits of quantification were 2, 0.5, and 5 pg/mg for molidustat, roxadustat, and vadadustat, respectively. The analysis of the athlete's head hair (collected 1 month after the urine test) showed a concentration of molidustat of 135 pg/mg, and his beard hair and his fingernails clippings contained 55 and 40 pg/mg, respectively.

01 Dec 2024·Cellular and Molecular Life Sciences

Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress

Article

Author: Diaz, Olivier ; Perrin-Cocon, Laure ; Lalande, Alexandre ; Jacquemin, Clémence ; Mathieu, Cyrille ; Aublin-Gex, Anne ; Toesca, Johan ; El Orch, Walid ; Jacolin, Florentine ; Si-Tahar, Mustapha ; Vidalain, Pierre-Olivier ; Lotteau, Vincent

AbstractThe hypoxia response pathway enables adaptation to oxygen deprivation. It is mediated by hypoxia-inducible factors (HIF), which promote metabolic reprogramming, erythropoiesis, angiogenesis and tissue remodeling. This led to the successful development of HIF-inducing drugs for treating anemia and some of these molecules are now in clinic. However, elevated levels of HIFs are frequently associated with tumor growth, poor prognosis, and drug resistance in various cancers, including hepatocellular carcinoma (HCC). Consequently, there are concerns regarding the recommendation of HIF-inducing drugs in certain clinical situations. Here, we analyzed the effects of two HIF-inducing drugs, Molidustat and Roxadustat, in the well-characterized HCC cell line Huh7. These drugs increased HIF-1α and HIF-2α protein levels which both participate in inducing hypoxia response genes such as BNIP3, SERPINE1, LDHA or EPO. Combined transcriptomics, proteomics and metabolomics showed that Molidustat increased the expression of glycolytic enzymes, while the mitochondrial network was fragmented and cellular respiration decreased. This metabolic remodeling was associated with a reduced proliferation and a lower demand for pyrimidine supply, but an increased ability of cells to convert pyruvate to lactate. This was accompanied by a higher resistance to the inhibition of mitochondrial respiration by antimycin A, a phenotype confirmed in Roxadustat-treated Huh7 cells and Molidustat-treated hepatoblastoma cells (Huh6 and HepG2). Overall, this study shows that HIF-inducing drugs increase the metabolic resilience of liver cancer cells to metabolic stressors, arguing for careful monitoring of patients treated with HIF-inducing drugs, especially when they are at risk of liver cancer.

01 Nov 2024·Clinical and Experimental Nephrology

The comparison of four hypoxia-inducible factor prolyl hydroxylase inhibitors on drug potency and cost for treatment in patients with renal anemia

Article

Author: Imai, Atsuhiro ; Imai, Enyu

BACKGROUNDFive hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved for marketing in Japan. However, marked differences exist in terms of drug potency, dose requirement, and pharmacokinetics.METHODSThe primary evaluation in this study was the changes in hemoglobin levels, dose escalation, drug potency, and cost among HIF-PHIs, 3 months after the initiation of treatment.RESULTSAll patients treated with HIF-PHI between August 2020 and December 2023 were enrolled in this study. In total, 124 patients were administered daprodustat (N = 37), enarodustat (N = 44), molidustat (N = 13), or vadadustat (N = 30). The mean hemoglobin levels of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 11.7 g/dL, 11.8 g/dL, 12.2 g/dL, and 11.3 g/dL, respectively. At 3 months, the mean doses of daprodustat, enarodustat, molidustat, and vadadustat increased by 110%, 177%, 125%, and 152%, respectively, from the initial dose. The HIF-PHI potency indices (HPI) of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 0.168, 0.307, 0.184, and 0.254, respectively. At 3 months, the mean daily costs of daprodustat, enarodustat, molidustat, and vadadustat were JPY 345, JPY 434, JPY 206, and JPY 565, respectively.CONCLUSIONThe difference in dose escalation for anemia treatment among HIF-PHIs is due to differences in drug potency, where the HPI significantly differs among HIF-PHIs. The disparity between the HPI and the cost of the initial dose accounts for the variance in the daily costs of renal anemia treatment among HIF-PHIs.

100 Deals associated with Molidustat Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
D11273	-	B03XA	DB15642

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Anemia in chronic kidney disease	Japan	Bayer AG	22 Jan 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Anemia of renal disease	Discovery	Japan	Bayer AG	12 Dec 2017
Anemia	Discovery	United States	Bayer AG	28 Oct 2013
Chronic Kidney Diseases	Discovery	United States	Bayer AG	28 Oct 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03350347 (MIYABI ND-M, Pubmed \| Am J Nephrol) Manual	Phase 3	Anemia	164	molidustat	(pwhvcrsuhx) = hfswfkbnth qktzfzxugv (qyuzpvrufp, 11.48 - 11.85) View more	Non-inferior	16 Sep 2021
				darbepoetin alfa	(pwhvcrsuhx) = qcxflvzvhp qktzfzxugv (qyuzpvrufp, 11.31 - 11.74) View more
NCT03350321 (MIYABI ND-C, Pubmed \| Am J Nephrol) Manual	Phase 3	Anemia	162	Molidustat	(avcrldflyw) = ilssyqehfz kitlkqthum (xaaxdyprvw, 11.07 - 11.50) View more	Positive	16 Sep 2021
				ESA darbepoetin alfa	(avcrldflyw) = cvspscssxm kitlkqthum (xaaxdyprvw, 11.50 - 11.90) View more
NCT03418168 (Pubmed \| Ther Apher Dial) Manual	Phase 3	Anemia	51	Molidustat	(ujfbufzaxn) = ohsyyrcwqj bruxynvkle (vbxzuhuzdh, 40.3 - 68.9)	Positive	26 Jul 2021
MIYABI program (ERA2021)	Phase 3	Anemia	51	Molidustat 75 mg	dnswishgbb(htzijdsfxk) = wmqxgyhtyn pkrfxqqsbl (qkbpkqpiyh, 40.3 - 68.9)	Positive	29 May 2021
NCT03351166 (Pubmed \| Ther Apher Dial)	Phase 3	Anemia in chronic kidney disease	25	Molidustat	(nccqoymgkb) = cnltmqbnka colygtorfd (udxbmpeigh )	Positive	27 Jan 2021
NCT03350347 (MIYABI ND-M, ERA2020)	Phase 3	Anemia of renal disease	-	Molidustat	kexiiwiuvu(npwpaomqqc) = trugemvary usfmndnzrb (eucdghgmho, 11.48 - 11.85) View more	Positive	07 Jun 2020
				Darbepoetin alfa	seyknzurtm(dkspgekuwt) = sqglsfmzwg wcwracrktp (hoelcwvczr, 12.33)
NCT03350321 (MIYABI ND-C, ERA2020)	Phase 3	Anemia of renal disease erythropoietin	-	Molidustat	aiblmyrrup(bsdrztfrsj) = liomsefwdx nyjbxzikfd (qoseeuwnvu, 11.07 - 11.50)	Positive	07 Jun 2020
				Darbepoetin alfa	aiblmyrrup(bsdrztfrsj) = alvmncqhvk nyjbxzikfd (qoseeuwnvu )
ERA2018	Phase 2	Chronic Kidney Diseases	101	Molidustat	woeswaroqq(fapciniypf) = an increase in TIBC values were observed in the molidustat group tcnylwrfnw (yhdtkjhfma ) View more	Positive	18 May 2018
				Placebo
ERA2016	Not Applicable	Anemia in chronic kidney disease	-	Molidustat 25 mg	(owmrhsaqua) = Treatment emergent adverse events (TEAE) were reported in 69.6% of molidustat treated subjects and in 53.1% of subjects on darbepoetin umfgdqzkog (xgebblifbk ) View more	-	14 May 2016
				Molidustat 50 mg
SO036 (ERA2016)	Phase 2	Chronic Kidney Diseases	121	Molidustat 25mg once daily	(omthfilnvb) = Treatment emergent adverse events (TEAE) were reported in 66.3% of all molidustat treated subjects and in 80% of subjects on placebo nrudxykcyy (rnmefpcped ) View more	Positive	14 May 2016
				Molidustat 50mg once daily