2. Anti-infection
  3. Flavivirus Virus Protease Dengue Virus
  4. JMX0207

JMX0207 is an orally active flavivirus NS2B-NS3 protease inhibitor. JMX0207 showed an IC50-SLC of 1.3 μM for blocking NS2B-NS3 protein interaction and an IC50-pro of 8.2 μM for inhibiting protease catalytic activity.. JMX0207 directly binds viral NS3 protease at the NS2B-NS3 interface with a Kd of 1.1 μM, blocks viral polyprotein precursor processing, suppresses viral RNA replication and viral protein production. JMX0207 can be used for the study of Zika virus infection and Dengue virus infection.

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JMX0207

JMX0207 Chemical Structure

CAS No. : 33580-97-1

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JMX0207 Related Antibodies

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Description

JMX0207 is an orally active flavivirus NS2B-NS3 protease inhibitor. JMX0207 showed an IC50-SLC of 1.3 μM for blocking NS2B-NS3 protein interaction and an IC50-pro of 8.2 μM for inhibiting protease catalytic activity.. JMX0207 directly binds viral NS3 protease at the NS2B-NS3 interface with a Kd of 1.1 μM, blocks viral polyprotein precursor processing, suppresses viral RNA replication and viral protein production. JMX0207 can be used for the study of Zika virus infection and Dengue virus infection[1].

IC50 & Target[1]

DENV2 NS2B-NS3 protease

 

DENV2 NS3 protease

1.1 μM (Kd)

In Vitro

JMX0207 inhibits the molecular interaction between viral NS3 and its cofactor NS2B in the split luciferase complementation assay, with an IC50-SLC of 1.3 μM[1].
JMX0207 inhibits DENV2 NS2B-NS3 activity with an IC50-pro of 8.2 μM[1].
JMX0207 directly binds viral NS3 protease with a Kd of 1.1 μM in the SPR assay, and protein thermal shift assay shows that JMX0207 binding stabilizes viral NS3 protease with a 0.75 ℃ increase in Tm[1].
JMX0207 (0.01-10 μM; 48 h) inhibits DENV2 infectivity in A549 cells with an EC50-DN2 of 0.31 μM, and shows a CC50 of 31.9 μM[1].
JMX0207 (0.19-5 μM) reduces ZIKV RNA copy number and viral E antigen production in ZIKV-infected A549 cells in a dose-dependent manner, with an EC50-ZK of 0.30 μM[1].
JMX0207 (0.03-7.5 μM) reduces ZIKV viral protein expression and viral RNA synthesis in human neural progenitor cells (HNPCs) in a dose-dependent manner[1].
JMX0207 (1.5 μM) protects iPSC-derived 3D mini-brain organoids from ZIKV infection and reduces ZIKV production[1].
JMX0207 (0.75 μM; 0-24 h) remains effective when added up to 24 h postinfection, indicating that JMX0207 inhibits viral replication rather than viral entry[1].
JMX0207 inhibits DENV2 replication in a DENV2 replicon cell line with an EC50-DN2 of 1.1 μM[1].
JMX0207 (0.19-0.75 μM; 48 h postinfection) reduces ZIKV NS3 protein production and increases high-molecular-weight unprocessed viral polyprotein precursor in ZIKV-infected A549 cells in a dose-dependent manner[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

JMX0207 Related Antibodies

RT-PCR[1]

Cell Line: A549
Concentration: 0.19, 0.38, 0.75, 1.5, 5 μM
Incubation Time: 48 h postinfection
Result: Reduced ZIKV RNA copy number in a dose-dependent manner in ZIKV-infected A549 cells.

Immunofluorescence[1]

Cell Line: A549
Concentration: 0.19, 0.56, 1.67, 5 μM
Incubation Time: 48 h postinfection
Result: Reduced ZIKV viral E protein production in a dose-dependent manner, as shown by pan-flavivirus anti-E 4G2 antibody staining.

Western Blot Analysis[1]

Cell Line: A549
Concentration: 0.19, 0.38, 0.75 μM
Incubation Time: 48 h postinfection
Result: Reduced ZIKV NS3 protein production in a dose-dependent manner.
Increased accumulation of high-molecular-weight unprocessed viral polyprotein precursor recognized by anti-ZIKV NS3 antibody.
Supported inhibition of viral protease function and viral polyprotein precursor processing.

Immunofluorescence[1]

Cell Line: iPSC-derived 3D mini-brain organoids
Concentration: 1.5 μM
Incubation Time: 5 dpi for PFU assay; 7 dpi for fluorescence imaging
Result: Showed no obvious toxic effect on 3D organoids and maintained organoid morphology.
Nearly completely protected 3D mini-brain organoids from ZIKV infection.
Reduced ZIKV antigen production across organoid layers and significantly decreased ZIKV production from the organoids.
Parmacokinetics
Species Dose Route Tmax Cmax T1/2 AUC0-∞
Mice[1] 40 mg/kg p.o. 1.2 h 145 μM 11 h 2719 μM/L·h
In Vivo

JMX0207 (20 mg/kg/day; p.o.; once daily; for 3 days postinfection) significantly reduces ZIKV-induced viremia in A129 mice inoculated with PRVABC59 ZIKV[1].
JMX0207 (40 mg/kg/day; p.o.; once daily; for 7 days) shows no signs of toxicity in mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Four-week-old A129 mice inoculated with 1.7 × 105 PFU PRVABC59 ZIKV[1]
Dosage: 20 mg/kg/day
Administration: Oral gavage (p.o.); once daily; for 3 days postinfection
Result: Significantly reduced ZIKV-induced viremia compared with vehicle control.
Viremia was measured by plaque forming unit (PFU) assay on day 3 postinfection.
Showed in vivo antiviral activity against ZIKV after oral administration.
Animal Model: Adult female B6 mice [1]
Dosage: 40 mg/kg/day
Administration: Oral gavage (p.o.); once daily; for 7 days
Result: Displayed no sign of toxicity during repeated oral dosing.
Supported low toxicity and acceptable in vivo tolerability at 40 mg/kg/day.
Molecular Weight

337.67

Formula

C13H8ClN3O6
CAS No.
SMILES

O=C(C1=CC=CC([N+]([O-])=O)=C1O)NC2=CC=C([N+]([O-])=O)C=C2Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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JMX0207 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

JMX020733580-97-1JMX 0207JMX-0207FlavivirusVirus ProteaseDengue VirusDENVZika virusDengue virusDENV2ZIKVviral NS3 proteaseNS2B-NS3 interactionviral polyprotein precursor processingA549HNPChuman neural progenitor cellsiPSC-derived 3D mini-brain organoidsDENV2 replicon cell lineviral RNAviral E proteinviral NS3 proteinA129 ZIKV mouse modelPRVABC59viremiaoral gavageimproved pharmacokineticsInhibitorinhibitorinhibit

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