FM-74-103
FM-74-103 is a selective GSPT1 PROTAC degrader and broad-spectrum antiviral agent. FM-74-103 recruits GSPT1 to the Cereblon E3 ligase to form a ternary complex, thereby driving GSPT1 ubiquitination and proteasomal degradation. FM-74-103 inhibits the replication of IAV, SARS-CoV-2 and CMV (including Nucleozin (HY-50001)-resistant influenza A virus). FM-74-103 can be used in research related to influenza A virus infection, SARS-CoV-2 infection and cytomegalovirus infection.
(Pink: GSPT1 ligand (HY-50001); Blue: Cereblon ligand (HY-138793); Black: linker).
For research use only. We do not sell to patients.
- Formula: C39H39ClN6O8
- Molecular Weight:755.22
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
eRF3a/GSPT1 |
Cereblon |
In Vitro
FM-74-103 selectively degrades GSPT1 in cells and potently inhibits the replication of various viruses, including Nucleozin-resistant IAV, SARS-CoV-2 in A549-ACE2 cells, and CMV, with extremely low cytotoxicity[1].
FM-74-103 (1 μM) reduces the levels of all SARS-CoV-2 viral proteins in infected A549-ACE2 cells and downregulates the expression of GSPT1 and eRF1[2].
FM-74-103 (1 μM; 3 h pre-infection and 24 h post infection) inhibits the replication of AD169BADrUL131 virus in ARPE-19 cells by degrading GSPT1/eRF1 and inducing eIF2α phosphorylation, with no significant cytotoxicity[2].
FM-74-103 (1 μM; 3 h pre-infection and 24 h post infection) inhibits SARS-CoV-2 replication in 3D lung organoids, which is confirmed by the reduction in SARS-CoV-2 NP levels[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:ARPE-19 cells infected with AD169BADrUL131 (GFP-expressing CMV) virus
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Concentration:1 μM
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Incubation Time:3 h pre-infection and 24 h post infection
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Result:Inhibit AD169BADrUL131 virus replication (reduced GFP fluorescence) in cells strongly.
Not reduce cell viability significantly.
Degrade GSPT1/eRF1 complex.
Induce integrated stress response (ISR) via phosphorylation of eIF2α, while total eIF2α levels remain constant.
Chemical Information
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Molecular Weight 755.22
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Formula C39H39ClN6O8
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SMILES
ClC1=CC([N+]([O-])=O)=CC=C1N2CCN(CC2)C(C3=C(ON=C3C4=C(C=CC=C4)OCCCCCC5=CC=C6C(CN(C6=O)C7C(NC(CC7)=O)=O)=C5)C)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Research Protocol for Infectious Diseases
Infectious-disease experiments test how pathogens interact with host barriers, innate immune receptors, inflammatory signaling, pathogen replication, and tissue injury; pattern-recognition receptors such as TLRs, RIG-I-like receptors, NOD-like receptors, and inflammasomes detect microbial molecules and activate NF-κB, interferon, and cytokine responses. The central hypothesis is that infection severity reflects the balance between pathogen burden and host response: protective inflammation restricts pathogen growth, whereas excessive or mislocalized inflammation contributes to tissue damage and disease phenotype. Unresolved questions include which host pathways are protective versus pathogenic, why some infection models fail to translate to human disease, and which combined readouts best predict clinically relevant infection outcomes.
Purity & Documentation
References
[1]. Jin J, et al. PROTACs in Antivirals: Current Advancements and Future Perspectives. Molecules. 2025;30(16):3402. Published 2025 Aug 18. [Content Brief]
[2]. Zhao N, et al. Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics. Cell Host Microbe. 2023;31(7):1154-1169.e10. [Content Brief]
[3]. An Q, et al. New strategies to enhance the efficiency and precision of drug discovery. Front Pharmacol. 2025;16:1550158. Published 2025 Feb 11. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)