TMP1
TMP1 is an orally active bispecific inhibitor of M pro (IC50 = 312.5 nM)/TMPRSS2 (IC50 = 1.28 μM, KD = 10.10 μM). TMP1 exhibits broad protection against different SARS-CoV-2 variants in vitro. TMP1 cross-protects against highly pathogenic coronaviruses (SARS-CoV-1, SARS-CoV-2, and MERS-CoV) in vivo and effectively blocks the transmission of SARS-CoV-2. TMP1 can inhibit infection by SARS-CoV-2 escape mutants that are resistant to Nivolumab (HY-P9903). TMP1 can be used in coronavirus research.
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- Fòrmula: C36H43ClF3N5O5
- Peso molecular:718.21
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
TMP1 (48 h) has no cytotoxicity against wild-type SARS-CoV-2 and other variants (VOCs), including Alpha, Beta, Delta, and Omicron (BA.1 and JN.1), in VeroE6-TMPRSS2 cells, reduced viral gene copy number and virus titer in human nasal epithelial cells (ALI-hNEC) infected with SARS-CoV-2 Omicron subtypes JN.1 and KP.2[1].
TMP1 (0-20 μM, 24 h) reduces both viral burden and infectious progeny viral titres in VeroE6, VeroE6-TMPRSS2, and LLC-MK2 cells were conducted in the presence of 2 µM P-gp inhibitor CP-100356 (HY-108347)[1].
TMP1 (0-50 μM, 24-48 h) inhibits the replication of seasonal HCoVs (HCoV-HKU1, -OC43, -NL63 and -229E) with EC50 ranging from 0.31 to 2.60 µM, cross-protects against highly-pathogenic coronaviruses SARS-CoV-1 and MERS-CoV with the EC50 of 0.55 and 5.26 µM[1].
TMP1 (1-50 μM) inhibits TMPRSS2-dependent cell-cell fusion mediated by the SARS-CoV-2 wild-type spike[1].
TMP1 inhibits recombinant the Mpro of SARS-CoV-2, SARS-CoV-1 and MERS-CoV, with IC50s of 0.313, 0.516 and 74.6 μM[1].
TMP1 (0-50 μM) reduces SARS-CoV-2, SARS-CoV-1, and MERS-CoV replication in TMPRSS-2-deficient VeroE6 cells[1].
TMP1 reduces the intracellular viral gene copies of rSARS-CoV-2 NSP5-E166V, resulting in EC50 of 0.449 μM in rSARS-CoV-2 NSP5-E166V infected Calu3 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
TMP1 (90 mg/kg, o.p., once) is against the prevalent Omicron lineage in the human upper airway epithelium and effectively attenuates SARS-CoV-2 transmission in PFU SARS-CoV-2 Delta-infected golden syrian hamsters model[1].
TMP1 (100-150 mg/kg, o.p., twice per day, 4 days) confers broad-spectrum antiviral protection against SARS-CoV-1-infected heterozygous mice and MERS-CoVMA-infected heterozygous hDPP4-KI mice[1].
TMP1 (100 mg/kg, o.p., twice per day, 4 days) interacts with Mpro using a distinct mechanism when compared with NRV, therefore retaining the sensitivity in rSARS-CoV-2 NSP5-E166V-infected heterozygous K18-hACE2 C57BL/6 J mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SARS-CoV-2-infected (500-1250 PFU) heterozygous K18-hACE2 C57BL/6 J mice (6-12-week-old)[1]
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Dosage:100 mg/kg
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Administration:o.p., twice per day, 4 days
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Result:Could be maintained at 11.1-, 11.4- and 6.5-fold higher than its in vitro EC50 of SARS-CoV-2 Delta.
Suppressed SARS-CoV-2 infection, reduced viral burdens in the lung tissues, the expression of N protein, alleviated or absent loss of epithelium integrity, septal inflammation, alveoli deformation, and submucosal inflammatory infiltrations.
Delayed onset of death, rescued the survival rate, lowered viral gene copies by 7.3- and 9.2-fold in the nasal turbinate and lung tissues, respectively.
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Animal Model:SARS-CoV-2 Delta-infected 2000 PFU) golden syrian hamsters (8-10-week-old) model[1]
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Dosage:90 mg/kg
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Administration:o.p., once
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Result:Reduced viral gene copies in the exposed nasal canal, infectious virus titers, viral load in lung tissue, and viral N protein expression, alleviated the massive inflammatory infiltration in the alveolar septa and alveolar deformation.
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Animal Model:SARS-CoV-1-infected (500 PFU) heterozygous K18-hACE2 C57BL/6 J mice (6-12-week-old)[1]
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Dosage:100 mg/kg
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Administration:o.p., twice per day, 4 days
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Result:Reduced viral load and SARS-CoV-1 nucleocapsid protein expression in nasal turbinates and lung tissues, titers of infectious viral progeny in the lungs, and alleviated loss of nasal mucosal epithelial integrity and alveolar damage.
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Animal Model:MERS-CoVMA-infected (500 PFU) heterozygous hDPP4-KI C57BL/6 J mice (6-12-week-old)[1]
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Dosage:150 mg/kg
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Administration:o.p., twice per day, 4 days
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Result:Suppressed MERS-CoVMA replication in both nasal turbinates and lungs, decreased infectious viral titres and expression of MERS-CoVMA N protein in the nasal turbinate and lung tissues. Alleviated virus-induced epithelial damage in the nasal turbinate and reduced alveolar destruction.
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Animal Model:RSARS-CoV-2 NSP5-E166V-infected heterozygous K18-hACE2 C57BL/6 J mice (6-12-week-old)[1]
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Dosage:100 mg/kg
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Administration:o.p., twice per day, 4 days
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Result:Reduced infectious virus titers in nasal turbinates and lung tissues, viral antigens in nasal turbinates, N protein expression in infected lung tissue samples, and ameliorated virus-induced pathological changes.
Chemical Information
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Peso molecular 718.21
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Fòrmula C36H43ClF3N5O5
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SMILES
O=C(C([C@H](NC([C@@H]1C[C@H](CN1C([C@H](C2CCCCC2)NC(C3CCC(F)(CC3)F)=O)=O)F)=O)CC4=CC=CC=C4)=O)NCC5=NC=C(C=C5)Cl
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TMP1 Related Classifications
HY-175344 Related Classifications
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