Chemistry:FRM-0334

From HandWiki

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

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

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

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "FRM 0334". 25 January 2024. https://adisinsight.springer.com/drugs/800030069. 
  2. ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on EVP-0334 with Synapse". 8 May 2025. https://synapse.patsnap.com/drug/e4f00f6f98374097824db79811f113ca. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "FRM-0334". 27 June 2016. https://www.alzforum.org/therapeutics/frm-0334. 
  4. ↑ 4.0 4.1 4.2 4.3 "Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs". Expert Opinion on Pharmacotherapy 20 (9): 1091–1107. June 2019. doi:10.1080/14656566.2019.1598377. PMID 31002267. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "Poster: Development of the novel histone deacetylase inhibitor EVP-0334 for CNS indications". 38th Annual Meeting of the Society for Neuroscience. November 2008. 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. ↑ 6.0 6.1 6.2 "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. September 2021. doi:10.1001/jamanetworkopen.2021.25584. PMID 34559230. 
  7. ↑ 7.0 7.1 "The histone deacetylase inhibitor EVP-0334 is pro-cognitive in mice". 38th Annual Meeting for the Society of Neuroscience. 2008. 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. 



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