Wikipedia

Vafidemstat

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]

Vafidemstat
Clinical data
Other namesORY-2001; ORY2001
Routes of
administration		Oral[1][2]
Drug classLysine-specific demethylase 1 (LSD1) inhibitor; Monoamine oxidase B (MAO-B) inhibitor[1]
Identifiers
  • 5-[[[(1R,2S)-2-(4-phenylmethoxyphenyl)cyclopropyl]amino]methyl]-1,3,4-oxadiazol-2-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC19H20N4O2
Molar mass336.395 g·mol−1
3D model (JSmol)
  • C1[C@H]([C@@H]1NCC2=NN=C(O2)N)C3=CC=C(C=C3)OCC4=CC=CC=C4
  • 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

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

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  1. ^ a b c d e f g h "Vafidemstat - Oryzon Genomics". AdisInsight. 9 October 2024. Retrieved 6 November 2024.
  2. ^ a b c 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. ^ a b "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.
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