Chemistry:T-5224

From HandWiki

T-5224 is a small-molecule c-Fos/activator protein 1 (AP-1) inhibitor which was under development for the treatment of rheumatoid arthritis but was never marketed.[1][2][3] It is taken orally.[1] The drug was under development by Toyama Chemical.[1][2] It reached phase 2 clinical trials prior to the discontinuation of its development.[1][2]

T-5524 has been found to selectively inhibit FOS-containing AP-1 complexes.[4][5][3] An analogous kind of approach might be useful for targeting a subset of ΔFosB-associated complexes to treat conditions like addiction.[4] The activity of T-5224 itself against ΔFosB is unknown.[5]

References

  1. ↑ 1.0 1.1 1.2 1.3 "T 5224". AdisInsight. Springer Nature Switzerland AG. 29 October 2018. https://adisinsight.springer.com/drugs/800016746. 
  2. ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on T-5224 with Synapse". Synapse. PatSnap. 7 June 2025. https://synapse.patsnap.com/drug/dd6e4b00f59640f7adccf90f34c20106. 
  3. ↑ 3.0 3.1 "Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1". Nature Biotechnology 26 (7): 817–823. July 2008. doi:10.1038/nbt1412. PMID 18587386. 
  4. ↑ 4.0 4.1 "ΔFOSB: A Potentially Druggable Master Orchestrator of Activity-Dependent Gene Expression". ACS Chemical Neuroscience 13 (3): 296–307. February 2022. doi:10.1021/acschemneuro.1c00723. PMID 35020364. "As we have described, ΔFOSB is expressed in many different cell types and tissues in response to stimuli both natural and artificial, and its functions range from mediating responses to psychotropic drugs, to controlling stress susceptibility vs resilience, to facilitating learning and memory, to transforming bone cells to drive tumor growth, and beyond. As such, ΔFOSB has often been questioned as a viable target for therapeutic intervention in the many disease states with which it is associated due to presumptive concerns of side effects in any of these diverse areas of function. However, it has become apparent that TFs with a similar diversity of functions and gene targets are viable pharmacological targets for the treatment of disease.128 One of the clearest examples of this advance has been the selective inhibition of FOS-containing AP1 complexes by the drug T-5224. This compound has been proven to be effective in reversing arthritis and spinal cartilage degeneration in preclinical mouse models,35,36 and Toyoma Chemical has entered this compound in Phase II trials for the treatment of rheumatoid arthritis.". 
  5. ↑ 5.0 5.1 "Small molecule screening identifies regulators of the transcription factor ΔFosB". ACS Chemical Neuroscience 3 (7): 546–556. July 2012. doi:10.1021/cn3000235. PMID 22860224. "Recent studies show that a number of transcription factors can be regulated with small molecules.30,31 [...] While small molecule inhibitors of c-Fos-containing AP-1 complexes are known, such as curcumin,35 tanshinone IIA,36 and nordihydroguaiaretic acid,37 these are not active against ΔFosB or JunD-containing species (tested up to 100 μM, results not shown). A benzophenone derivative in preclinical trials to resolve arthritis, T-5224, also inhibits c-Fos and c-Jun-containing AP-1 activity, though the mechanism of action and its activity against ΔFosB are not known.38". 



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