MRLB-223
MRLB-223 is a preferential HDAC1 and HDAC2 inhibitor with activity against tumor cells.MRLB-223 induces histone hyperacetylation, intrinsic apoptotic pathway activation, tumor cell apoptosis, Hsp90 hyperacetylation, and caspase-dependent Bcr-Abl degradation.MRLB-223 mediates p53-independent tumor cell death, with activity suppressed by Bcl-2 overexpression, and kills Bcr-Abl-expressing myeloid cells.MRLB-223 exerts effects in mice bearing Eμ-myc lymphomas.MRLB-223 can be used for the research of Eμ-myc lymphoma.
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- No. CAS: 937727-03-2
- Fòrmula: C23H23N5O3S
- Peso molecular:449.53
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Almacenamiento:
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Actividad biológica
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HDAC1 |
HDAC2 |
HSP90 |
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Cell Line
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Type | Value | Description | References |
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| HCT-116 | GI50 |
97 nM
Compound: 2
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Growth inhibition of human HCT116 cells after 96 hrs
Growth inhibition of human HCT116 cells after 96 hrs
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[PMID: 24900838] |
| HCT-116 | IC50 |
400 nM
Compound: 2
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Inhibition of HDAC in human HCT116 cells assessed as plasma drug level causing increase in H2BK5 acetylation after 24 hrs by ELISA
Inhibition of HDAC in human HCT116 cells assessed as plasma drug level causing increase in H2BK5 acetylation after 24 hrs by ELISA
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[PMID: 24900838] |
| HEK293 | IC50 |
>30 μM
Compound: 2
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Inhibition of human ERG expressed in HEK cells by voltage clamp assay
Inhibition of human ERG expressed in HEK cells by voltage clamp assay
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[PMID: 24900838] |
| HEL | GI50 |
120 nM
Compound: 2
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Growth inhibition of HEL cells after 96 hrs
Growth inhibition of HEL cells after 96 hrs
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[PMID: 24900838] |
| Jurkat | GI50 |
110 nM
Compound: 2
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Growth inhibition of human Jurkat cells after 96 hrs
Growth inhibition of human Jurkat cells after 96 hrs
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[PMID: 24900838] |
| Sf9 | IC50 |
45 nM
Compound: 2
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Inhibition of FLAG-tagged full-length human recombinant HDAC2 expressed in baculovirus infected Sf9 cells using acetyl-lysine containing peptide as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by fluorescence as
Inhibition of FLAG-tagged full-length human recombinant HDAC2 expressed in baculovirus infected Sf9 cells using acetyl-lysine containing peptide as substrate preincubated for 10 mins followed by substrate addition measured after 60 mins by fluorescence as
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[PMID: 24900838] |
MRLB-223 (0.2-10 μM; 24-48 h) induces concentration-dependent apoptosis in Eμ-myc lymphoma cells via the intrinsic apoptotic pathway with delayed kinetics, with an IC70 of 5 μM at 24 hours and 0.5 μM at 48 hours[1].
MRLB-223 (0-12 μM; 24 h) induces concentration-dependent apoptosis in Eμ-myc and Eμ-myc/p53-/- lymphoma cells independently of p53, while overexpression of Bcl-2 blocks this apoptotic effect[1].
MRLB-223 (0-30 μM; 24-72 h) induces concentration-dependent cell death in FDCP-1 mouse myeloid cells with delayed kinetics, requiring longer incubation times for maximal effect[1].
MRLB-223 (0-26 μM; 72 h) induces concentration-dependent cell death in FDCP-1/Bcr-Abl and FDCP-1/Bcr-AblT315I cells with delayed kinetics, and Bcr-Abl degradation occurs as a downstream consequence of caspase-mediated apoptosis[1].
MRLB-223 (10 μM; 24 h) induces hyperacetylation of Hsp90 in FDCP-1/Bcr-Abl cells despite lacking activity against HDAC6[1].
MRLB-223 (0-16 μM; 72 h) induces concentration-dependent cell death in FDCP-1/Bcr-Abl cells, and knockdown of HDAC6 does not enhance this apoptotic effect[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Eμ-myc, Eμ-myc/p53-/-, and Eμ-myc/Bcl-2 lymphoma cells
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Concentration:0-12 μM
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Incubation Time:24 h
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Result:Induced concentration-dependent PI uptake in Eμ-myc and Eμ-myc/p53-/- cells, with both cell lines showing similar sensitivity.
Suppressed MRLB-223-mediated tumor cell death was observed when Bcl-2 was overexpressed.
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Cell Line:FDCP-1/Bcr-Abl and FDCP-1/Bcr-Abl(T315I) mouse myeloid cells
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Concentration:0-26 μM (72 h PI uptake assay); 5, 10 μM (48 h Bcr-Abl degradation assay)
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Incubation Time:72 h (PI uptake assay); 48 h (Bcr-Abl degradation assay)
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Result:Induced concentration-dependent PI uptake in FDCP-1/Bcr-Abl and FDCP-1/Bcr-Abl(T315I) cells at 72 hours, with both cell lines showing equivalent sensitivity.
Induced Bcr-Abl degradation concomitant with apoptosis in cells treated with 5 or 10 μM for 48 hours.
Suppressed apoptosis and maintained Bcr-Abl expression when co-treated with the caspase inhibitor Q-VD-OPh for 48 hours.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (6- to 8-week-old; injected intravenously with 5×105 Eμ-myc lymphoma cells)[1]
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Dosage:15 mg/kg (therapy studies; in vivo apoptosis assays; FDG-PET analysis)
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Administration:i.p.; daily, continuous (therapy studies); single dose (in vivo apoptosis assays; FDG-PET analysis)
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Result:Reduced average peripheral white blood cell counts to 23.9×103/μL by day 21 and 33.8×103/μL by day 35 (vehicle controls reached 39.2×103/μL by day 21).
Increased median mouse survival to 42 days (vehicle controls had 33 days).
Induced delayed histone H3 and H4 hyperacetylation in lymphoma cells, with minimal acetylation at 2 hours post-dose and gradual increases over time.
Showed no reduction in lymph node FDG uptake at 4 hours post-dose, but a decrease was observed by 48 hours post-dose.
Chemical Information
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No. CAS 937727-03-2
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Peso molecular 449.53
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Fòrmula C23H23N5O3S
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SMILES
O=C1OC2(CCN(CC2)C3=NC=C(C(NC4=C(N)C=CC(C5=CC=CS5)=C4)=O)C=C3)CN1
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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)
MRLB-223 Related Classifications
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