Vafidemstat

Vafidemstat

Clinical data
Other names	ORY-2001; ORY2001
Routes of administration	Oral[1][2]
Drug class	Lysine-specific demethylase 1 (LSD1) inhibitor; Monoamine oxidase B (MAO-B) inhibitor[1]
Identifiers
IUPAC name 5-[[[(1R,2S)-2-(4-phenylmethoxyphenyl)cyclopropyl]amino]methyl]-1,3,4-oxadiazol-2-amine
CAS Number	1357362-02-7
PubChem CID	66714983
DrugBank	DB16446
ChemSpider	68019508
UNII	LZ82JLT4UP
ChEMBL	ChEMBL4802155
Chemical and physical data
Formula	C19H20N4O2
Molar mass	336.395 g·mol^−1
3D model (JSmol)	Interactive image
SMILES C1[C@H]([C@@H]1NCC2=NN=C(O2)N)C3=CC=C(C=C3)OCC4=CC=CC=C4
InChI InChI=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 Key:XBBRLCXCBCZIOI-DLBZAZTESA-N

Vafidemstat (INNTooltip 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.^[1][3][2] It is or was also being developed for several other indications, but no recent development has been reported for these uses.^[1] The drug is taken by mouth.^[1]

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.^[1] Conversely, no recent development has been reported for autism, dementia, Huntington's disease, Parkinson's disease, and telomeric 22q13 monosomy syndrome.^[1] It is being developed by Oryzon.^[1][3]

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).^[2][4] Another drug, zavondemstat (QC8222, TACH101), is a pan-inhibitor of lysine-specific demethylase 4 (LSD4; KDM4).^[5][6][7] Vafidemstat contains the chemical structure of (1S,2R)-tranylcypromine within its own structure.^[8]

References

1. "Vafidemstat - Oryzon Genomics". AdisInsight. 9 October 2024. Retrieved 6 November 2024.
2. Noce B, Di Bello E, Fioravanti R, Mai A (2023). "LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials". Front Pharmacol. 14: 1120911. doi:10.3389/fphar.2023.1120911. PMC 9932783. PMID 36817147.
3. "Delving into the Latest Updates on Vafidemstat with Synapse". Synapse. 1 November 2024. Retrieved 6 November 2024.
4. Johnson JD, Alejo S, Jayamohan S, Sareddy GR (2023). "Lysine-specific demethylase 1 as a therapeutic cancer target: observations from preclinical study". Expert Opin Ther Targets. 27 (12): 1177–1188. doi:10.1080/14728222.2023.2288277. PMC 10872912. PMID 37997756.
5. 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.
6. "Delving into the Latest Updates on Zavondemstat with Synapse". Synapse. 1 November 2024. Retrieved 6 November 2024.
7. World Health Organization (2024). "Use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances, 2024" (PDF). World Health Organization. p. 184. Retrieved 21 October 2024. -stat- or enzyme inhibitors -stat [...] -demstat lysine-specific histone demethylase inhibitors (a) bomedemstat (122), iadademstat (119), pulrodemstat (124), seclidemstat (118), vafidemstat (119), zavondemstat (128)
8. "Vafidemstat". PubChem. Retrieved 7 November 2024.