JSF-3285
JSF-3285 is an orally active KasA inhibitor of Mycobacterium tuberculosis (Kd = 70.7 nM). JSF-3285 inhibits KasA in the FAS-II mycolic acid biosynthesis pathway and is active against both drug-susceptible and multidrug-resistant Mycobacterium tuberculosis. JSF-3285 exhibits bactericidal efficacy in acute and chronic mouse models of tuberculosis infection. JSF-3285 significantly enhances the bactericidal and sterilizing efficacy of the Bedaquiline (HY-14881)-Pretomanid (HY-10844) combination regimen in a mouse relapse model of infection. JSF-3285 can be used for research related to tuberculosis.
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- CAS No.: 2293983-99-8
- Formule: C12H16FN3O2S
- Masse moléculaire:285.34
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Activité biologique
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Vero | CC50 |
170 μM
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Cytotoxicity against African green monkey Vero cells assessed by MTT viability assay.
Cytotoxicity against African green monkey Vero cells assessed by MTT viability assay.
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32197094 |
| J774.A1 | IC50 |
0.046 μM
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Inhibition of intracellular M. tuberculosis mc2 6206 growth in J774A.1 mouse macrophages incubated 48 hrs measured by CFU counting and luciferase activity.
Inhibition of intracellular M. tuberculosis mc2 6206 growth in J774A.1 mouse macrophages incubated 48 hrs measured by CFU counting and luciferase activity.
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32197094 |
In Vitro
JSF-3285 inhibits the growth of Mycobacterium tuberculosis mc2 6206 in J774A.1 macrophages with an IC50 of 0.046 µM; it inhibits mycolic acid biosynthesis in Mycobacterium tuberculosis H37Rv and in the G200A and L205P kasA mutants; it lacks significant in vitro activity against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter cloacae, with MIC >50 mg/mL[1].
JSF-3285 selects drug-resistant Mycobacterium tuberculosis H37Rv at frequencies of 9.3 × 10-8 to 2.7 × 10-8, and the resistance mutations are located in kasA[1].
JSF-3285 inhibits Mycobacterium tuberculosis H37Rv with a geometric mean MIC of 0.095 μg/mL and retains activity against isogenic inhA promoter (−8T→A) and katG M1A mutants, with an MIC of 0.12 μg/mL for both[3].
JSF‑3285 (molecular docking) has a binding energy of -6.98 Kcal/mol with KasA, and a Ki value of 10.5 μM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
JSF-3285 (1-30 mg/kg; intragastric p.o.; once daily, 5 days per week; 4 weeks) shows dose-dependent bactericidal activity in a subacute mouse tuberculosis model, with an ED90 of 4.2 mg/kg/day[3].
JSF-3285 (18-600 mg/kg/week, with combination dosing at 3-100 mg/kg; intragastric p.o.; BID, QD, or QOD, 6 days per week, or once daily, 5 days per week; 3 weeks) mainly exhibits bacteriostatic activity as monotherapy in acute mouse tuberculosis and enhances the activity of the BPa regimen (Bedaquiline (HY-14881)-Pretomanid (HY-10844))[3].
JSF-3285 (30 mg/kg; intragastric p.o.; once daily, 5 days per week; 1.5-2.5 months) enhances the bactericidal activity of multiple dosing regimens and shortens the regimen duration required to prevent relapse in a mouse tuberculosis relapse model[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (BALB/cAnNCrl; female; 9 weeks old; 18-20 g)[1]
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Dosage:100, 200 mg/kg qd
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Administration:p.o.; qd; 4 weeks
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Result:Reduced lung CFU burden by 2 log10 was achieved after 4 weeks of dosing for both the 100 mg/kg and 200 mg/kg qd regimens relative to the baseline bacterial burden at the start of dosing.
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Animal Model:BALB/c (BALB/cAnNCrl; female; 9 weeks old; 18-20 g)[1]
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Dosage:20, 50, 100, 200 mg/kg
200 mg/kg (alone, with INH (HY-B0329) 10 mg/kg, with RIF (HY-B0272) 10 mg/kg) -
Administration:p.o.; qd; 4 weeks
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Result:Achieved substantial lung CFU reductions of 1.5‑2.0 log_10 after 4‑week JSF‑3285 treatment; its monotherapy outperformed INH/RIF, combination use boosted first‑line drug efficacy, 20‑200 mg/kg groups showed comparable effects while 20 mg/kg was superior to 5 and 10 mg/kg.
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Animal Model:BALB/c (BALB/cAnNCrl; female; 9 weeks old; 18-20 g)[1]
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Dosage:200 mg/kg qd; 20 mg/kg qd; 20 mg/kg bid; 10 mg/kg qd; 5 mg/kg qd
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Administration:p.o.; qd or bid; 4 weeks
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Result:Reduced lung CFUs by 1.5‑2.0 log10 after four‑week treatment with JSF‑3285 at doses of 200‑5 mg/kg qd and 20 mg/kg qd or bid.
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Animal Model:BALB/c (female, 6 weeks old)[3]
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Dosage:1, 3, 10, and 30 mg/kg
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Administration:p.o. by gavage; once daily, 5 days per week; 4 weeks
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Result:Observed dose‑dependent lung CFU alterations for JSF‑3285 in the subacute murine TB model; the 1 mg/kg group exhibited a 0.68 log10 CFU increase relative to D0, whereas 3‑30 mg/kg doses triggered CFU reduction, and yielded QD ED50 of 1.5 mg/kg and ED90 of 4.2 mg/kg.
Chemical Information
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CAS No. 2293983-99-8
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Masse moléculaire 285.34
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Formule C12H16FN3O2S
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SMILES
O=S(NC1=CC2=C(NN=C2C)C=C1)(CCCCF)=O
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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)
JSF-3285 Related Classifications
HY-187941 Related Classifications
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