CZL-149
CZL-149 is an orally active dual BET and p300/CBP bromodomains inhibitor with IC50s of 13 nM and 10.5 nM for BED4 BD1 and p300, respectively. CZL-149 reduces c-Myc and H3K27Ac levels. CZL-149 has good drug-like properties and metabolic characteristics, as well as good safety. CZL-149 can be used for the study of multiple myeloma.
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- No. CAS: 3094772-96-7
- Fòrmula: C23H23F3N4O3
- Peso molecular:460.45
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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p300 10.5 nM (IC50, TSA Assay) |
BRD4 BD1 13 nM (IC50, AlphaScreen Assay) |
BRD4 BD2 78 nM (IC50, AlphaScreen Assay) |
BRD4 BD1 2 nM (IC50, HTRF Assay) |
BRD4 BD2 22 nM (IC50, HTRF Assay) |
CBP 183 nM (IC50, AlphaScreen Assay) |
p300 118 nM (IC50, AlphaScreen Assay) |
Thermal displacement analysis (TSA) showed that CZL-149 (compound 14) inhibits the p300 bromine domain with an IC50 of 10.5 nM[1].
AlphaScreen analysis showed that CZL-149 exhibits strong inhibitory activity against BRD4 BD1 (IC50: 10 nM) and BRD4 BD2 (IC50: 80 nM)[1].
CZL-149 (6 days) shows antiproliferative activity against OPM-2 cells, with an IC50 value of 3.3 nM[1].
CZL-149 binds most strongly to BET family proteins (BRD2/3/4/T), followed by CECR2 and p300/CBP[1].
AlphaScreen results shows that CZL-149 inhibits BRD4 BD1 and BD2 with IC50 values of 13 nM and 78 nM, respectively; and inhibits p300 and CBP bromodomain with IC50 values of 118 nM and 183 nM, respectively. HTRF results showed that CZL-149 has a strong inhibitory effect on BRD4 BD1 and BD2, with IC50 values of 2 nM and 22 nM, respectively[1].
In OPM-2 cells, CZL-149 (50 nM; 72 h) significantly downregulates the expression of AGAP7P, SLC3A2, VAT1, SLC1A5, LONP1, AARS1, GADD45A, VEGFA, SESN2 and DBN1 genes[1].
In OPM-2 cells, CZL-149 (10-50 nM) inhibits c-Myc and H3K27Ac levels in a dose-dependent manner[1].
CZL-149 exhibits high microsomal stability in mouse, rat and human liver microsomes, with half-lives of 145 minutes (mouse), 205 minutes (rat) and 118 minutes (human), respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
CZL-149 (10 mg/kg; p.o.; once daily; for 7 days) displays an improved safety profile in C57BL/6 mice[1].
CZL-149 (20 mg/kg; oral; single dose) accumulates primarily in the liver in mice, with low levels detected in the heart and brain[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice were injected subcutaneously with 5 × 106 OPM-2 cells[1].
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Dosage:10 mg/kg
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Administration:p.o.; once daily; for 21 days
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Result:Significantly suppressed tumor growth, achieving a tumor growth inhibition (TGI) of 78%.
Showed better tolerated in mice.
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Animal Model:Female C57BL/6 mice (6-8 weeks)[1].
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Dosage:10 mg/kg
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Administration:p.o.; once daily; for 7 days
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Result:Did not cause a significant reduction in platelet count.
Showed good hematological safety.
Chemical Information
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No. CAS 3094772-96-7
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Peso molecular 460.45
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Fòrmula C23H23F3N4O3
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SMILES
O=C1C2=C(C(C3=CC4=C(N=C(C5CCOCC5)N4CCOC(F)(F)F)C=C3)=CN1C)C=CN2
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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)
CZL-149 Related Classifications
HY-183992 Related Classifications
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