Frenolicin B
Frenolicin B is a covalent enzyme inhibitor and an orally active antiparasitic agent, with an IC50 of 0.2 μM against human Prx1. Frenolicin B selectively inhibits Glutaredoxin 3 via covalent modification of the active-site cysteines Cys159/Cys261. Frenolicin B selectively inhibits Peroxiredoxin 1 via covalent modification of the active-site cysteines Cys83/Cys173. Frenolicin B can be used in research related to colon cancer, breast cancer, lung cancer and malaria.
For research use only. We do not sell to patients.
- CAS No.: 68930-68-7
- Formula: C18H16O6
- Molecular Weight:328.32
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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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Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
0.28 μM
Compound: 7
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Cytotoxicity against human A549 cells after 2 days by MTT assay
Cytotoxicity against human A549 cells after 2 days by MTT assay
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[PMID: 23944931] |
| MDA-MB-468 | IC50 |
0.06 μM
Compound: 3, frenolicin
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Cytotoxicity against human MDA468 cells expressing AKT
Cytotoxicity against human MDA468 cells expressing AKT
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[PMID: 19309081] |
In Vitro
Frenolicin B (0.032-30 μM; 15 min room temperature incubation) is a potent, selective inhibitor of purified recombinant human Prx1, with an apparent IC50 of 0.2 μM, inhibition kinetics parameters kᵢ = 0.65 μM and kᵢₙₐcₜ = 0.02 min-1, and ~20-fold higher potency against Prx1 than Prx2[1].
Frenolicin B (1-10 μM; 1 h pre-incubation) directly engages Prx1 and Grx3 in HCT116 colon cancer cell lysates and with purified recombinant proteins, as demonstrated by competitive binding with an active biotinylated probe[1].
Frenolicin B (200 μM; 2 h 37 °C incubation) covalently modifies the active site cysteines Cys83/Cys173 of purified recombinant human Prx1 and Cys159/Cys261 of purified recombinant human Grx3, which are essential for ligand binding[1].
Frenolicin B (2 μM; 12 h post-transfection incubation) inhibits cap-dependent translation in a 4E-BP1-dependent manner in HCT116 human colon cancer cells[1].
Frenolicin B (72 h incubation) exhibits preferential cytotoxicity against human cancer cell lines (colon, breast, lung) with IC50 values ranging from 50 nM to 130 nM after 72 h incubation, compared to non-malignant cells with higher IC50 values[1].
Frenolicin B (2 μM; 3 h incubation) increases extracellular H2O2 levels and at 2 μM for 1 h increases intracellular ROS levels in HCT116 human colon cancer cells, with ROS induction reversible by NAC pre-treatment[1].
Frenolicin B (0.2-2 μM; 12 h incubation) dose-dependently inhibits mTORC1-mediated 4E-BP1 phosphorylation at T37/46, S65, and T70, and induces apoptosis (cleaved PARP) in HCT116 human colon cancer cells, with these effects reversed by NAC pre-treatment[1].
Frenolicin B (0.002-80 μM; 72 h) inhibits in vitro growth of Plasmodium falciparum HB3, Dd2, and 7G8 strains with IC50 values of 600 ± 100 nM, 800 ± 200 nM, and 800 ± 150 nM, respectively, and incubation with selected human cytochrome P450 enzymes either maintains or improves its antiparasitic potency[2].
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:HCT116 human colon cancer cell; purified recombinant human Prx1/Grx3 proteins
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Concentration:1-10 μM (Frenolicin B, HCT116 lysate pre-incubation); 1-2 μM (probe 1)
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Incubation Time:1 h (Frenolicin B pre-incubation with HCT116 lysates); 1 h (probe 1 incubation)
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Result:Competed with active probe 1 for binding to Prx1 and Grx3 in HCT116 lysates.
Confirmed direct binding to pure recombinant Prx1 and Grx3 via probe 1 labeling.
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Cell Line:HCT116 human colon cancer cells
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Concentration:0.2-2 μM; 400 μM (NAC pre-treatment)
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Incubation Time:12 h (phosphorylation analysis); 6 h (NAC reversal analysis); 1 h (NAC pre-treatment)
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Result:Dose-dependently inhibited phosphorylation of 4E-BP1 at T37/46, S65, and T70.
Induced cleaved PARP (apoptotic marker).
Had inhibition of 4E-BP1 phosphorylation and induction of cleaved PARP reversed by pre-treatment with NAC.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD1 mice (8-week-old)[2]
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Dosage:10 mg/kg; 20 mg/kg; 40 mg/kg; 63 mg/kg
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Administration:p.o.; daily; 4 days
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Result:Reduced mean parasitemia to 39 % and cured 0/5 mice at 10 mg/kg.
Reduced mean parasitemia to 37 % and cured 0/5 mice at 20 mg/kg.
Reduced mean parasitemia to 33 % and cured 1/5 mice at 40 mg/kg.
Reduced mean parasitemia to 15% (a >50% reduction relative to vehicle control) and cured 2/5 mice at 63 mg/kg.
Chemical Information
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CAS No. 68930-68-7
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Molecular Weight 328.32
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Formula C18H16O6
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SMILES
O=C1C2=C(C(C3=C(O)C=CC=C31)=O)[C@H](O[C@@]4([H])[C@]2([H])OC(C4)=O)CCC
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Structure Classification
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Initial Source
S. roseofulvus.
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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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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.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
References
[1]. Ye Q, et al. Frenolicin B Targets Peroxiredoxin 1 and Glutaredoxin 3 to Trigger ROS/4E-BP1-Mediated Antitumor Effects. Cell Chem Biol. 2019 Mar 21;26(3):366-377.e12. [Content Brief]
[2]. Fitzgerald JT, et al. In vitro and in vivo activity of frenolicin B against Plasmodium falciparum and P berghei. J Antibiot (Tokyo). 2011 Dec;64(12):799-801. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Frenolicin B Related Classifications
HY-W671129 Related Classifications
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