// Workers AI · dad joke modeWhat did FRM-0334 say to its date? "You're a great format.
| Clinical data | |
|---|---|
| Other names | FROM0334; EVP-0334; EVP0334 |
| Routes of administration | Oral[1] |
| Drug class | Histone deacetylase inhibitor |
| ATC code |
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| 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]
Pharmacology
[edit]The drug is a selective inhibitor of a subset of class I and class II HDACs, with IC50 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]
History
[edit]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 2 3 4 5 6 7 "FRM 0334". AdisInsight. 25 January 2024. Retrieved 2 August 2026.
- 1 2 3 "Delving into the Latest Updates on EVP-0334 with Synapse". Synapse. 8 May 2025. Retrieved 2 August 2026.
- 1 2 3 4 5 6 7 8 "FRM-0334". ALZFORUM. 27 June 2016. Retrieved 2 August 2026.
- 1 2 3 4 Logroscino G, Imbimbo BP, Lozupone M, Sardone R, Capozzo R, Battista P, et al. (June 2019). "Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs". Expert Opinion on Pharmacotherapy. 20 (9): 1091–1107. doi:10.1080/14656566.2019.1598377. PMID 31002267.
- 1 2 3 4 5 6 Patzke H, Albayya F, Besterman J (November 2008). Poster: Development of the novel histone deacetylase inhibitor EVP-0334 for CNS indications. 38th Annual Meeting of the Society for Neuroscience.
- 1 2 3 Ljubenkov PA, Edwards L, Iaccarino L, La Joie R, Rojas JC, Koestler M, et 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 Network Open. 4 (9): e2125584. doi:10.1001/jamanetworkopen.2021.25584. PMC 8463943. PMID 34559230.
- 1 2 Leventhal L, Tran A, Gallager I (2008). The histone deacetylase inhibitor EVP-0334 is pro-cognitive in mice. 38th Annual Meeting for the Society of Neuroscience.