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// Workers AI · dad joke modeWhat did FRM-0334 say to its date? You're a great format.

From Wikipedia, the free encyclopedia
FRM-0334
Clinical data
Other namesFROM0334; EVP-0334; EVP0334
Routes of
administration
Oral[1]
Drug classHistone deacetylase inhibitor
ATC code
  • None
Identifiers
PubChem SID

FRM-0334, also known as EVP-0334, is a histone deacetylase (HDAC) inhibitor which was under development for the treatment of frontotemporal dementia (FTD), Alzheimer's disease, and Parkinson's disease but was never marketed.[1][2][3][4] It is taken orally.[1]

The drug is a selective inhibitor of a subset of class I and class II HDACs, with IC50Tooltip half-maximal inhibitory concentration values in the nanomolar range.[4][3][5] The pharmacokinetics of FRM-0334 in animals and humans have been studied.[4][6][5] It efficiently crosses into the brain in rodents.[3][5] The drug has been found to enhance cognition and memory in rodents.[4][3][5][7] Based on preclinical research, it was expected to increase progranulin (PRGN) levels to help treat FTD.[3][6]

FRM-0334 was first described in the scientific literature by 2008.[5][7] It was developed to overcome various limitations of existing HDAC inhibitors like sodium butyrate and valproic acid (low potency and selectivity), vorinostat (SAHA) (poor brain permeability), and trichostatin A (TSA) (genotoxicity) for central nervous system (CNS) disorders.[5] The drug was developed by MethylGene, EnVivo Pharmaceuticals (later renamed to FORUM Pharmaceuticals), and Mirati Therapeutics.[1][2][3] It reached phase 2 clinical trials prior to the discontinuation of its development.[1][2] A phase 2 trial found the drug to be ineffective, possibly due to insufficient drug exposure.[3][6] Development was discontinued in 2016 or 2018.[1][3] The chemical structure of FRM-0334 does not appear to have been disclosed.[1]

See also

[edit]

References

[edit]
  1. 1 2 3 4 5 6 7 "FRM 0334". AdisInsight. 25 January 2024. Retrieved 2 August 2026.
  2. 1 2 3 "Delving into the Latest Updates on EVP-0334 with Synapse". Synapse. 8 May 2025. Retrieved 2 August 2026.
  3. 1 2 3 4 5 6 7 8 "FRM-0334". ALZFORUM. 27 June 2016. Retrieved 2 August 2026.
  4. 1 2 3 4 Logroscino G, Imbimbo BP, Lozupone M, Sardone R, Capozzo R, Battista P, Zecca C, Dibello V, Giannelli G, Bellomo A, Greco A, Daniele A, Seripa D, Panza F (June 2019). "Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs". Expert Opin Pharmacother. 20 (9): 1091–1107. doi:10.1080/14656566.2019.1598377. PMID 31002267.
  5. 1 2 3 4 5 6 Patzke, H., Albayya, F., & Besterman, J. (2008, November). Development of the novel histone deacetylase inhibitor EVP-0334 for CNS indications. In Poster presented at: 38th Annual Meeting of the Society for Neuroscience. https://www.abstractsonline.com/plan/ViewAbstract.aspx?mID=1981&sKey=7608b1d6-24c8-4a0d-85e8-68357f77ef82&cKey=b58f0420-5bde-407b-afe3-948d274e708b&mKey=afea068d-d012-4520-8e42-10e4d1af7944
  6. 1 2 3 Ljubenkov PA, Edwards L, Iaccarino L, La Joie R, Rojas JC, Koestler M, Harris B, Boeve BF, Borroni B, van Swieten JC, Grossman M, Pasquier F, Frisoni GB, Mummery CJ, Vandenberghe R, Le Ber I, Hannequin D, McGinnis SM, Auriacombe S, Onofrj M, Goodman IJ, Riordan HJ, Wisniewski G, Hesterman J, Marek K, Haynes BA, Patzke H, Koenig G, Hilt D, Moebius H, Boxer AL (September 2021). "Effect of the Histone Deacetylase Inhibitor FRM-0334 on Progranulin Levels in Patients With Progranulin Gene Haploinsufficiency: A Randomized Clinical Trial". JAMA Netw Open. 4 (9): e2125584. doi:10.1001/jamanetworkopen.2021.25584. PMC 8463943. PMID 34559230.
  7. 1 2 Leventhal, L., Tran, A., & Gallager, I. (2008). The histone deacetylase inhibitor EVP-0334 is pro-cognitive in mice. In 38th Annual Meeting for the Society of Neuroscience. https://www.abstractsonline.com/plan/ViewAbstract.aspx?mID=1981&sKey=7608b1d6-24c8-4a0d-85e8-68357f77ef82&cKey=4256d6f9-3c58-4903-83ed-8d46d22972dd&mKey=afea068d-d012-4520-8e42-10e4d1af7944