TDI-015051
TDI-015051 is a highly selective, orally active antiviral agent that targets the coronavirus NSP14 guanine-N7 methyltransferase. TDI-015051 binds to substrates in a non-competitive manner and forms a stable ternary complex, precisely blocking the capping and methylation processes of viral mRNA. TDI-015051 potently inhibits a variety of coronaviruses (including SARS-CoV-2 and MERS). By impairing viral replication and translation and inducing a moderate type I interferon-mediated immune response, it significantly reduces pulmonary viral load and exhibits a synergistic effect with Nirmatrelvir (HY-138687). In addition, TDI-015051 does not inhibit non-coronavirus methyltransferases, and the drug-resistant mutations it induces impair viral fitness, demonstrating excellent antiviral properties and safety. TDI-015051 can be used for research on COVID-19 and the replication mechanism of coronaviruses.The IC50 values of TDI-015051 against SARS-CoV-2, α-hCoV-NL63, α-hCoV-229E, β-hCoV-MERS are 0.15 nM, 1.7 nM, 2.6 nM and 3.6 nM, respectively, and the Ka value against SARS-CoV-2 is 0.061 nM.
For research use only. We do not sell to patients.
- CAS No.: 3052313-73-9
- Formula: C22H22FN5O4S
- Molecular Weight:471.50
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
All DNA Methyltransferase Isoforms
More
Biological Activity
Description
IC50 & Target
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CYP3A4 20 nM (IC50) |
In Vitro
TDI-015051 (dose-response format) potently inhibits SARS-CoV-2 NSP14 guanine-N7 methyltransferase activity in a biochemical assay with an IC50 ≤ 0.15 nM[1].
TDI-015051 inhibits SARS-CoV-2 infection in Huh-7.5 cells with an EC50 of 11.4 nM, and this activity is potentiated to an EC50 of 0.8 nM by co-treatment with 5 μM DZNeP, with no cytotoxicity at concentrations ≤ 3 μM[1].
TDI-015051 (0.1-16 nM; 4 days post-infection) completely inhibits SARS-CoV-2 replication in human primary small airway epithelial cells at concentrations ≥ 4 nM[1].
TDI-015051 (dose-response format; 1 h pre-treatment; 24 h, 48 h, 72 h post-infection evaluation) inhibits SARS-CoV-2 infection in Vero E6 cells with EC50 values of 99.5 nM, 71.1 nM, and 52.4 nM at 24 h, 48 h, and 72 h post-infection, respectively, following 1 h pre-treatment[1].
TDI-015051 (dose-response format) inhibits infection by multiple human coronaviruses in cell-based assays, with EC50 values of 0.12 μM for α-hCoV-NL63, 3.7 μM for α-hCoV-229E, and 6.5 μM for β-hCoV-MERS, with no detectable cytotoxicity at the tested concentrations[1].
TDI-015051 (dose-response format) does not inhibit SARS-CoV-2 NSP16-NSP10, human RNMT-RAM, or Zika virus NS5 methyltransferases, demonstrating selective activity against coronavirus NSP14[1].
TDI-015051 (1 μM; 1 h pre-treatment, 24 h infection) treatment of SARS-CoV-2-infected A549-ACE2-TMPRSS2 cells induces a weak type I interferon-mediated immune response via increased interferon-stimulated gene expression[1].
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:A549-ACE2-TMPRSS2 cells
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Concentration:1 μM
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Incubation Time:1 h (pre-treatment); 24 h (infection)
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Result:Induced a moderate increase in expression of interferon-stimulated genes including RSAD2, IFI6, IRF7, IFIT2, and OAS1 compared to DMSO-treated infected cells.
Parmacokinetics
In Vivo
Treatment with TDI-015051 (500 mg/kg; p.o.; twice daily; 4 days) initiated 1 h prior to infection in mice reduces the SARS-CoV-2 lung viral titer in K18-hACE2 mice by one order of magnitude, with efficacy comparable to that of Nirmatrelvir (HY-138687).
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:K18-hACE2 transgenic mice with COVID-19 (6-8 weeks old, male and female, SARS-CoV-2 infected)[1]
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Dosage:150 mg/kg; 500 mg/kg
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Administration:p.o.; twice daily; 4 days
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Result:Reduced lung viral titres by approximately 2 orders of magnitude (confirmed by TCID50, PFU, and RT-qPCR assays).
Prevented substantial wei ght loss over the 4-day treatment period.
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Animal Model:K18-hACE2 transgenic mice with COVID-19 (6-8 weeks old, male and female, SARS-CoV-2 infected)[1]
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Dosage:500 mg/kg
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Administration:p.o.; twice daily; 4 days
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Result:Reduced lung viral titres by an order of magnitude higher than post-infection dosing (confirmed by TCID50, PFU, and RT-qPCR assays).
Induced statistically significant decreases in viral titres relative to vehicle controls.
Chemical Information
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CAS No. 3052313-73-9
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Molecular Weight 471.50
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Formula C22H22FN5O4S
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SMILES
O=S(N(CC1)CC2=C1NN=C2)(C3=C(C)N(C)C(C(NCC4=C(F)C=CC5=C4C=CO5)=O)=C3)=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.
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TDI-015051 Related Classifications
HY-170524 Related Classifications
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