MB-32
MB-32 is a potent and selective allosteric inhibitor of human angiotensin-converting enzyme 2 (hACE2) with a Kd value of 7.078 μM. MB-32 binds to a non-catalytic surface pocket on the N-terminal helix of ACE2, disrupts the interaction between ACE2 and the receptor-binding domain of SARS-CoV-2 spike protein through allosteric action, and preserves the enzymatic activity of ACE2 across different species. MB-32 achieves high concentrations in the airway via intranasal administration, with no detected cardiovascular toxicity. MB-32 can be used for research on coronavirus disease 2019.
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- Formule: C26H30N8O3S
- Masse moléculaire:534.63
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Activité biologique
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ACE2 7.078 μM (Kd, SPR assay) |
MB-32 (0.4-10 μM (hACE2); 60-second association and 120-second dissociation phases) binds to recombinant human ACE2 with a KD value of 7.078 μM, and also binds to ACE2 homologs from various mammals with micromolar affinity[1].
MB-32 (5 μg/mL; 15-minute pre-incubation, followed by 1-hour co-incubation with spike) reduces the binding capacity of SARS-CoV-2 spike protein to human ACE2 on the surface of transiently transfected HEK293T cells, without affecting the expression level of ACE2[1].
The binding of MB-32 (0.4-20 μM; 60-second association and 120-second dissociation phases) to human ACE2 is strongly dependent on the P565 residue, with additional contributions from the Y83, Q86, Q98 and Q102 residues[1].
MB-32 (0.01-100 μM; assay duration) potently and selectively inhibits pan-sarbecovirus pseudovirus entry into HEK293T-ACE2 cells, with an IC50 of 105 nM against SARS-CoV-2 wild-type and a selectivity index of 183.8[1].
MB-32 (0.308-25 μg/mL; 24 hours) inhibits the multi-cycle replication of authentic SARS-CoV-2 variants of concern (VOCs) and SARS-CoV-1 in HEK293T-ACE2 cells, with a mean IC50 of 9.2 μM, and shows no cytotoxicity at concentrations up to 129 μM[1].
MB-32 (0-8 μM; pre-incubated with virus for 2 hours followed by 24-hour culture) selectively inhibits SARS-CoV-2 replication in Calu-3 cells, with an IC50 of 1.615 μM, and shows no activity against MERS-CoV[1].
MB-32 (17.5 μM; 30 minutes (TMPRSS2); 5 minutes (Cathepsin L)) does not inhibit the enzymatic activity of TMPRSS2 or Cathepsin L[1].
The inhibitory effect of MB-32 (0.01-100 μM; assay duration) on SARS-CoV-2 pseudovirus entry is attenuated in HEK293T cells expressing ACE2Y83F or ACE2Y83A ACE2 mutants, indicating that Y83 is critical for the antiviral activity of MB-32[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Calu-3
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Concentration:0.5, 1, 2, 4, 8 μM
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Incubation Time:24 h, following a 2 h viral inoculation period
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Result:Reduced the SARS-CoV-2 nucleocapsid gene level with an IC50 of 1.615 μM, while no measurable inhibition of MERS-CoV was observed under the same conditions.
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Cell Line:HEK293T-ACE2
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Concentration:5 μg/mL
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Incubation Time:15 min pretreatment followed by 1 h incubation
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Result:Reduced Spike binding and internalization without affecting transferrin receptor-mediated endocytosis.
MB-32 (400 μg per hamster; intranasal administration; single dose) protects golden hamsters from infection with the SARS-CoV-2 Omicron JN.1 strain[1].
MB-32 (350 nmol per hamster; intranasal administration; single dose) prevents contact transmission of SARS-CoV-2 XBB.1.5 in golden hamsters, reducing infectious viral titers and viral gene copy numbers in the lungs by >2 logs[1].
MB-32 (60 μg per mouse; intranasal administration; single dose; co-administered with virus) provides complete protection against lethal SARS-CoV-2 infection in K18-hACE2 mice, resulting in 100% mouse survival, near-complete inhibition of viral replication, and reduced pathological damage in the lungs[1].
MB-32 (200 μg per rat; intranasal administration; single dose) shows no obvious cardiovascular adverse effects in Sprague Dawley rats[1].
MB-32 (2.33 mg/kg, i.n., single dose) achieves high local exposure in male C57BL/6 mice, with AUClast values of 466,726 ng·h/g in nasal turbinates and 13,346 ng·h/g in lungs, while systemic exposure remains relatively low[1]
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:K18-hACE2 C57BL/6J transgenic (6-8-week-old male, intranasal challenge with 2.5 × 104 PFU SARS-CoV-2 Omicron BA.2)[1]
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Dosage:60 μg/mouse; 2.33 mg/kg
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Administration:i.n.; single dose
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Result:Preserved body weight.
Reduced viral RdRp gene copies in lungs by >2 logs.
Reduced viral NP gene copies by >2 logs.
Eliminated detectable viral N protein in lung tissue.
Prevented significant infection-related histopathological lesions.
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Animal Model:K18-hACE2 C57BL/6J transgenic (6-8-week-old male, intranasal challenge with 2.5 × 104 PFU SARS-CoV-2 Omicron BA.5)[1]
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Dosage:60 μg/mouse; 2.33 mg/kg
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Administration:i.n.; single dose
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Result:Prevented significant body weight loss.
Reduced viral RdRp gene copies in lungs by ~1.5 logs.
Reduced viral sgNP gene copies by ~1.5 logs.
Reduced viral N protein detection in lung tissue (2/4 positive vs. 4/4 positive in vehicle controls).
Prevented severe infection-related histopathological lesions.
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Animal Model:(8-week-old male, intranasal challenge with 1 × 105 PFU SARS-CoV-2 Omicron JN.1)[1]
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Dosage:400 μg/hamster; 2 mg/mL
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Administration:i.n.; single dose
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Result:Reduced lung viral loads compared to vehicle controls.
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Animal Model:(10-12-week-old male, COVID-19 contact transmission model with SARS-CoV-2 XBB.1.5)[1]
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Dosage:350 nmol/hamster
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Administration:i.n.; single dose
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Result:Reduced infectious viral titres in lungs by >2 logs (P<0.0001).
Reduced viral RdRp and sgNP gene copies in lungs by >2 logs (P<0.0001).
Eliminated detectable viral N protein in lung tissue.
Prevented severe infection-related histopathological lesions.
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Animal Model:K18-hACE2 C57BL/6J transgenic (6-8-week-old male, intranasal challenge with 4 × 103 PFU SARS-CoV-2 HKU-001a)[1]
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Dosage:60 μg/mouse
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Administration:i.n.; single dose; co-administered with virus
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Result:Maintained stable body weights.
Achieved 100% survival compared to 0% survival in vehicle controls.
Suppressed viral RdRp gene copies by ~4.4 × 105-fold in nasal turbinates.
Suppressed viral RdRp gene copies by ~8.6 × 104-fold in lungs.
Eliminated detectable infectious virus in nasal turbinates or lungs (limit of detection <10 PFU/mL).
Eliminated detectable viral N protein in lung tissue.
Alleviated severe histopathological lesions (bronchiolitis, vasculitis, alveolitis with inflammatory infiltrates and hemorrhage).
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Animal Model:Sprague Dawley (220 g male and female, cardiovascular safety assessment)[1]
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Dosage:200 μg/rat
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Administration:i.n.; single dose
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Result:Showed no significant abnormal changes in heart rate, blood pressure, or ECG parameters compared to pre-drug baselines or vehicle controls.
Chemical Information
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Masse moléculaire 534.63
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Formule C26H30N8O3S
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SMILES
CC1=CC=C(C=C1)C2=NC3=CC(NC(NCCN4C=C(N=C4C)[N+]([O-])=O)=O)=C(C=C3S2)N5CCN(CC5)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MB-32 Related Classifications
HY-184485 Related Classifications
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