{{Short description|Chemical compound}} {{Drugbox | image = Molidustat.svg | image_class = skin-invert-image | width = 200
<!--Clinical data--> | tradename = Varenzin-CA1 | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_category = | routes_of_administration = By mouth | ATC_prefix = B03 | ATC_suffix = XA09
<!-- Legal status --> | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> | legal_AU_comment = | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> | legal_BR_comment = | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Varenzin-CA1 FOI Summary" /> | legal_EU = | legal_EU_comment = | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above -->
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | CAS_number = 1154028-82-6 | CAS_number2 = 1375799-59-9 | CAS_supplemental = | PubChem = 59603622 | IUPHAR_ligand = | DrugBank = DB15642 | DrugBank2 = DBSALT002944 | ChemSpiderID = 30922476 | ChemSpiderID2 = 32699298 | UNII = 9JH486CZ13 | UNII2 = CI0NE7C96T | KEGG = D12122 | ChEBI = | ChEMBL = 3646118 | NIAID_ChemDB = | PDB_ligand = A1H | synonyms = Bay 85-3934
<!-- Chemical and physical data --> | IUPAC_name = 2-(6-Morpholin-4-ylpyrimidin-4-yl)-4-(triazol-1-yl)-1''H''-pyrazol-3-one | C=13 | H=14 | N=8 | O=2 | SMILES = C1COCCN1C2=NC=NC(=C2)N3C(=O)C(=CN3)N4C=CN=N4 | StdInChI=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 | StdInChIKey = IJMBOKOTALXLKS-UHFFFAOYSA-N }}
'''Molidustat''' is a drug which acts as an HIF prolyl-hydroxylase inhibitor and thereby increases endogenous production of erythropoietin, which stimulates production of hemoglobin and red blood cells. It is in Phase III clinical trials for the treatment of anemia caused by chronic kidney disease.<ref>{{cite journal | vauthors = Flamme I, Oehme F, Ellinghaus P, Jeske M, Keldenich J, Thuss U | title = Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat) stimulates erythropoietin production without hypertensive effects | journal = PLOS ONE | volume = 9 | issue = 11 | article-number = e111838 | year = 2014 | pmid = 25392999 | pmc = 4230943 | doi = 10.1371/journal.pone.0111838 | bibcode = 2014PLoSO...9k1838F | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gupta N, Wish JB | title = Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD | journal = American Journal of Kidney Diseases | volume = 69 | issue = 6 | pages = 815–826 | date = June 2017 | pmid = 28242135 | doi = 10.1053/j.ajkd.2016.12.011 | doi-access = free }}</ref> Due to its potential applications in athletic doping, it has also been incorporated into screens for performance-enhancing drugs.<ref>{{cite journal | vauthors = Dib J, Mongongu C, Buisson C, Molina A, Schänzer W, Thuss U, Thevis M | display-authors = 6 | title = Mass spectrometric characterization of the hypoxia-inducible factor (HIF) stabilizer drug candidate BAY 85-3934 (molidustat) and its glucuronidated metabolite BAY-348, and their implementation into routine doping controls | journal = Drug Testing and Analysis | volume = 9 | issue = 1 | pages = 61–67 | date = January 2017 | pmid = 27346747 | doi = 10.1002/dta.2011 }}</ref>
== Veterinary use == Molidustat is indicated for the control of nonregenerative anemia associated with chronic kidney disease in cats.<ref name="Varenzin-CA1 FOI Summary">{{Cite web |url=https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/13903 |title=Archived copy |access-date=2023-05-02 |archive-date=2023-05-02 |archive-url=https://web.archive.org/web/20230502030453/https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/13903 |url-status=live }}</ref><ref name="FDA PR 20230501">{{cite press release | title=FDA Conditionally Approves First Drug for Anemia in Cats with Chronic Kidney Disease | website=U.S. Food and Drug Administration | date=1 May 2023 | url=https://www.fda.gov/news-events/press-announcements/fda-conditionally-approves-first-drug-anemia-cats-chronic-kidney-disease | access-date=1 May 2023 | archive-date=1 May 2023 | archive-url=https://web.archive.org/web/20230501205946/https://www.fda.gov/news-events/press-announcements/fda-conditionally-approves-first-drug-anemia-cats-chronic-kidney-disease }} {{PD-notice}}</ref> The US Food and Drug Administration (FDA) conditionally approved it in May 2023.<ref name="FDA PR 20230501" />
The reasonable expectation of effectiveness of Molidustat was evaluated in a study conducted in two phases.<ref name="FDA PR 20230501" /> The first phase involved a multi-center, double-masked, randomized, placebo-controlled field effectiveness and safety study.<ref name="FDA PR 20230501" /> The second phase was an unmasked, optional continuation of the field study.<ref name="FDA PR 20230501" /> The study enrolled 23 cats from 4 to 17 years of age from various breeds or breed mixes diagnosed with nonregenerative anemia associated with chronic kidney disease.<ref name="FDA PR 20230501" /> The FDA granted conditional approval of Varenzin-CA1 to Elanco US Inc.<ref name="FDA PR 20230501" />
== References == {{Reflist}}
{{Antianemic preparations}}
Category:Cat medications Category:Pyrimidines Category:4-Morpholinyl compounds Category:Pyrazolones Category:Triazoles