ZX079
ZX079 is a dual BRD4 and CBP PROTAC degrader with a BRD4 DC50 value of 0.035 nM and a CBP DC50 value of < 0.02 nM. ZX079 induces dose- and time-dependent degradation of BRD4 and CBP proteins through recruitment of the cereblon E3 ligase. ZX079 induces apoptosis in MV4-11 and MOLM-13 cells, reduces tumor growth in an acute myeloid leukemia xenograft model. ZX079 can be used for the research of acute myeloid leukemia.
(Pink: BRD4 (BD1) and BRD4 (BD2) and CBP and p300 ligand (HY-181759); Blue: Cereblon ligand (HY-14658); Black: linker (HY-W105740)).
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- No. CAS: 3124583-65-6
- Fòrmula: C47H56F3N7O7
- Peso molecular:887.99
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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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Chemical Information
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Actividad biológica
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BRD4 0.035 nM (DC50) |
BRD4(1) 0.9 μM (IC50) |
BRD4(2) 0.5 μM (IC50) |
CBP |
p300 |
Caspase 3 |
Cereblon |
ZX079 (10k) (24 h) exhibits dose- and time-dependent degradation of BRD4 (DC50 = 0.035 nM), CBP, p300 and BRD3 (DC50 < 0.02 nM) without significant degradation of BRD2[1].
ZX079 (0.0001-100 μM) binds potently to BRD4 (1) (IC50 = 0.9 μM), BRD4 (2) (IC50 = 0.5 μM), and CBP bromodomains (IC50 = 1.2 μM) and effectively promotes BRD4-PROTAC-CRBN and CBP-PROTAC-CRBN ternary complex assembly[1].
ZX079 (0.02-200 nM; 96 h) exerts superior antiproliferative activity against MV4-11 cells (IC50 = 0.86 nM) and MOLM-13 cells, while it shows minimal cytotoxicity against normal HUVEC and L929 cells (tested at 0.001-10 μM)[1].
ZX079 (200 nM; 8 h) selectively depletes BRD4, BRD3, CBP, and p300 proteins in MV4-11 cells at the proteome-wide level
ZX079 (37-1000 nM; 48 h) induces apoptosis in MV4-11 and MOLM-13 cells in a dose-dependent manner, accompanied by increased cleavage of Caspase-3 and almost complete reduction of c-Myc protein expression at 2 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 and MOLM-13 acute myeloid leukemia cells, HUVEC, L929 normal cells
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Concentration:10-6, 10-4, 10-2, 100, 102 μM (MV4-11 and MOLM-13 cells); 0.01, 0.01, 0.1, 1, 10, 100 μM (HUVEC and L929 cells)
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Incubation Time:96 h (MV4-11 and MOLM-13 cells); 48 h (HUVEC and L929 cells)
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Result:Exhibited an IC50 of 0.86 nM in MV4-11 cells and 18.93 nM in MOLM-13 cells.
Exhibited minimal cytotoxicity toward HUVEC and L929 cells.
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Cell Line:MV4-11 acute myeloid leukemia cells
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Concentration:0.02, 0.2, 2.0, 20, 200 nM (24 h); 200 nM (time-course); 2 nM, 200 nM (24 h)
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Incubation Time:1 h, 2 h, 4 h, 8 h, 12 h, 24 h (time-course); 24 h (fixed time)
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Result:Achieved 95% degradation of BRD4 and 74% degradation of CBP at 2 nM after 24 h.
Achieved 98% degradation of BRD4 and 99% degradation of CBP at 200 nM after 24 h.
Induced rapid degradation of CBP within 2 h, with near-complete depletion by 4 h.
Reduced BRD4 levels in a time-dependent manner over 24 h.
Exhibited a DC50 of 0.035 nM for BRD4, < 0.02 nM for CBP, and < 0.02 nM each for p300 and BRD3.
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Cell Line:MV4-11 and MOLM-13 acute myeloid leukemia cells
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Concentration:37, 111, 333, 1000 nM
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Incubation Time:48 h
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Result:Potently induced apoptosis in a dose-dependent manner, achieving over 60% apoptosis at 37 nM in MV4-11 cells.
Led to markedly increased cleaved caspase-3 levels and almost completely reduced c-Myc protein expression in MV4-11 cells at 20 nM.
Induced dose-dependent apoptosis in MOLM-13 cells.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD SCID (female, 4 weeks old, subcutaneous xenograft model)[1]
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Dosage:2 mg/kg (twice weekly); 10 mg/kg (weekly)
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Administration:intraperitoneal injection; 21 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 93% with 2 mg/kg twice-weekly dose.
Achieved a TGI rate of 91% with 10 mg/kg weekly dose.
Caused no significant body weight loss compared to vehicle control.
Induced degradation of BRD4 and CBP proteins in harvested tumors.
Significantly reduced c-Myc protein expression relative to vehicle control.
Chemical Information
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No. CAS 3124583-65-6
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Peso molecular 887.99
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Fòrmula C47H56F3N7O7
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SMILES
O=C(NC(CC1)=O)C1N(C2=O)C(C(C2=C3)=CC=C3NCCCCCCCCCCCC(N(CC4)CCC4C5=NC6=CC=C(C(C=C7C)=CN(C)C7=O)C=C6N5CCOC(F)(F)F)=O)=O
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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
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Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ZX079 Related Classifications
HY-181854 Related Classifications
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