Vafidemstat

{{Short description|Experimental enzyme inhibitor}}

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| routes_of_administration = Oral

| class = Lysine-specific demethylase 1 (LSD1) inhibitor; Monoamine oxidase B (MAO-B) inhibitor

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| CAS_number = 1357362-02-7

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| PubChem = 66714983

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| DrugBank = DB16446

| ChemSpiderID = 68019508

| UNII = LZ82JLT4UP

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| ChEMBL = 4802155

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| synonyms = ORY-2001; ORY2001

| IUPAC_name = 5-[[[(1R,2S)-2-(4-phenylmethoxyphenyl)cyclopropyl]amino]methyl]-1,3,4-oxadiazol-2-amine

| C=19 | H=20 | N=4 | O=2

| SMILES = C1[C@H]([C@@H]1NCC2=NN=C(O2)N)C3=CC=C(C=C3)OCC4=CC=CC=C4

| StdInChI = 1S/C19H20N4O2/c20-19-23-22-18(25-19)11-21-17-10-16(17)14-6-8-15(9-7-14)24-12-13-4-2-1-3-5-13/h1-9,16-17,21H,10-12H2,(H2,20,23)/t16-,17+/m0/s1

| StdInChIKey = XBBRLCXCBCZIOI-DLBZAZTESA-N

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Vafidemstat ({{Abbrlink|INN|International Nonproprietary Name}}; developmental code name ORY-2001) is a dual inhibitor of the enzymes lysine-specific demethylase 1 (LSD1; KDM1A) and monoamine oxidase B (MAO-B) which is under development for the treatment of a variety of medical conditions, including aggression, Alzheimer's disease, borderline personality disorder, multiple sclerosis, acute respiratory disease in COVID-19 infection, and schizophrenia.{{cite web | title=Vafidemstat - Oryzon Genomics | website=AdisInsight | date=9 October 2024 | url=https://adisinsight.springer.com/drugs/800045069 | access-date=6 November 2024}}{{cite web | title=Delving into the Latest Updates on Vafidemstat with Synapse | website=Synapse | date=1 November 2024 | url=https://synapse.patsnap.com/drug/d1efe73e113c423ab01f4f69ebc37cc3 | access-date=6 November 2024}}{{cite journal | vauthors = Noce B, Di Bello E, Fioravanti R, Mai A | title = LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials | journal = Front Pharmacol | volume = 14 | issue = | pages = 1120911 | date = 2023 | pmid = 36817147 | pmc = 9932783 | doi = 10.3389/fphar.2023.1120911 | doi-access = free | url = }} It is or was also being developed for several other indications, but no recent development has been reported for these uses. The drug is taken by mouth.

As of October 2024, vafidemstat is in phase 2 clinical trials for aggression, Alzheimer's disease, borderline personality disorder, multiple sclerosis, COVID-19 acute respiratory disease, and schizophrenia. Conversely, no recent development has been reported for autism, dementia, Huntington's disease, Parkinson's disease, and telomeric 22q13 monosomy syndrome. It is being developed by Oryzon.

Other LSD1 inhibitors that are under development for medical use include bomedemstat (IMG-7289), iadademstat (ORY-1001), phenelzine (Nardil), pulrodemstat (CC-90011), seclidemstat (SP-2577), and tranylcypromine (Parnate).{{cite journal | vauthors = Johnson JD, Alejo S, Jayamohan S, Sareddy GR | title = Lysine-specific demethylase 1 as a therapeutic cancer target: observations from preclinical study | journal = Expert Opin Ther Targets | volume = 27 | issue = 12 | pages = 1177–1188 | date = 2023 | pmid = 37997756 | doi = 10.1080/14728222.2023.2288277 | pmc = 10872912 | url = }} Another drug, zavondemstat (QC8222, TACH101), is a pan-inhibitor of lysine-specific demethylase 4 (LSD4; KDM4).Chandhasin, C., Perabo, F., Dai, Y., DiMascio, L., Mehta, R. K., Hassan, M. K., & Nyati, M. K. (2024). 245 (PB233): Histone methylation changes of H3K9 and H3K36 in PBMCs as pharmacodynamic biomarkers for Zavondemstat (TACH101), a paninhibitor of KDM4 histone lysine demethylase. European Journal of Cancer, 211, 114763.{{cite web | title=Delving into the Latest Updates on Zavondemstat with Synapse | website=Synapse | date=1 November 2024 | url=https://synapse.patsnap.com/drug/4a42923b95bf4d3e974dc927c3557e63 | access-date=6 November 2024}}{{cite web | vauthors = ((World Health Organization)) | title=Use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances, 2024 | publisher = World Health Organization | date = 2024 | url=https://iris.who.int/bitstream/handle/10665/379226/9789240099388-eng.pdf#page=190 | access-date=21 October 2024 | page=184 | quote=-stat- or enzyme inhibitors -stat [...] -demstat lysine-specific histone demethylase inhibitors (a) bomedemstat (122), iadademstat (119), pulrodemstat (124), seclidemstat (118), vafidemstat (119), zavondemstat (128)}} Vafidemstat contains the chemical structure of (1S,2R)-tranylcypromine within its own structure.{{cite web | title=Vafidemstat | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/66714983 | access-date=7 November 2024}}