PARP1/BRD4-IN-4
PARP1/BRD4-IN-4 is a PARP1/BRD4 inhibitor (IC50 = 88.70 nM and 9.27 nM, respectively). PARP1/BRD4-IN-4 impairs PARP family catalysis and BET bromodomain function. PARP1/BRD4-IN-4 inhibits colony formation, migration, invasion, tumor growth, and lung metastasis by impairing DNA single-strand break repair, suppressing DNA repair gene transcription and oncogenic signaling, inducing DNA damage and cell cycle arrest/apoptosis (Apoptosis), disrupting homologous recombination repair, and reducing cJUN/CCL2-mediated macrophage recruitment, infiltration, and pro-tumor polarization. PARP1/BRD4-IN-4 can be used for research on breast cancer.
For research use only. We do not sell to patients.
- Formula: C47H39FN6O7S
- Molecular Weight:850.91
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
Description
PARP1/BRD4-IN-4 is a PARP1/BRD4 inhibitor (IC50 = 88.70 nM and 9.27 nM, respectively). PARP1/BRD4-IN-4 impairs PARP family catalysis and BET bromodomain function. PARP1/BRD4-IN-4 inhibits colony formation, migration, invasion, tumor growth, and lung metastasis by impairing DNA single-strand break repair, suppressing DNA repair gene transcription and oncogenic signaling, inducing DNA damage and cell cycle arrest/apoptosis (Apoptosis), disrupting homologous recombination repair, and reducing cJUN/CCL2-mediated macrophage recruitment, infiltration, and pro-tumor polarization. PARP1/BRD4-IN-4 can be used for research on breast cancer[1].
IC50 & Target
[1]|
BRD4 9.27 nM (IC50) |
PARP-1 88.70 nM (IC50) |
PARP |
BET |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
0.39 μM
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Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 72 hrs by MTT assay.
Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 72 hrs by MTT assay.
|
acs.jmedchem.6c01713 |
| KP-4 | IC50 |
0.21 μM
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Antiproliferative activity against human KP4 cells assessed as viability reduction incubated 72 hrs by MTT assay.
Antiproliferative activity against human KP4 cells assessed as viability reduction incubated 72 hrs by MTT assay.
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acs.jmedchem.6c01713 |
| MDA-MB-468 | IC50 |
0.06 μM
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Cytotoxicity against human MDA-MB-468 cells assessed as cell viability inhibition.
Cytotoxicity against human MDA-MB-468 cells assessed as cell viability inhibition.
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acs.jmedchem.6c01713 |
| MDA-MB-453 | IC50 |
0.07 μM
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Cytotoxicity against human MDA-MB-453 cells assessed as cell viability inhibition.
Cytotoxicity against human MDA-MB-453 cells assessed as cell viability inhibition.
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acs.jmedchem.6c01713 |
| MIA PaCa-2 | IC50 |
0.08 μM
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Cytotoxicity against human MIA PaCa-2 cells assessed as cell viability inhibition.
Cytotoxicity against human MIA PaCa-2 cells assessed as cell viability inhibition.
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acs.jmedchem.6c01713 |
| CAPAN-1 | IC50 |
0.23 μM
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Cytotoxicity against human Capan-1 cells assessed as cell viability inhibition.
Cytotoxicity against human Capan-1 cells assessed as cell viability inhibition.
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acs.jmedchem.6c01713 |
| SNU-16 | IC50 |
0.03 μM
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Cytotoxicity against human SNU-16 cells assessed as cell viability inhibition.
Cytotoxicity against human SNU-16 cells assessed as cell viability inhibition.
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acs.jmedchem.6c01713 |
| BALB/3T3 | IC50 |
9.41 μM
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Cytotoxicity against mouse BALB/3T3 cells assessed as cell viability inhibition.
Cytotoxicity against mouse BALB/3T3 cells assessed as cell viability inhibition.
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acs.jmedchem.6c01713 |
| RAW264.7 | IC50 |
50 μM
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Cytotoxicity against mouse RAW 264.7 cells assessed as cell viability inhibition with IC50 greater than 50 μM.
Cytotoxicity against mouse RAW 264.7 cells assessed as cell viability inhibition with IC50 greater than 50 μM.
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acs.jmedchem.6c01713 |
| THP-1 | IC50 |
0.74 μM
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Cytotoxicity against human THP-1 (M0) cells assessed as cell viability inhibition.
Cytotoxicity against human THP-1 (M0) cells assessed as cell viability inhibition.
|
acs.jmedchem.6c01713 |
In Vitro
Anti-cancerApoptosisCell Cycle RegulationInnate ImmunityOthers
Anti-cancer
PARP1/BRD4-IN-4 (compound D6) (dose-response experiment; 72 h) potently inhibits MDA-MB-231 and KP4 proliferation, with IC50 values of 0.39 µM and 0.21 µM, respectively[1].
PARP1/BRD4-IN-4 (1-10 µM; exposure at 42-62°C for 5 min) directly binds PARP1 and BRD4 in MDA-MB-231 cells, increasing their thermal stability[1].
PARP1/BRD4-IN-4 (1 µM; 3 days) induces DNA damage in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.5 µM) inhibits HRR-related proteins and BRD4/c-Myc signaling in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.25-0.5 µM) reduces BRCA1, CtIP, and BRD4 mRNA levels in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.25-0.5 µM) reduces JUN and CCL2 mRNA levels in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.025-0.05 µM in MDA-MB-231, 0.5-1 µM in KP4; 14 days) inhibits colony formation in MDA-MB-231 and KP4 cells[1].
PARP1/BRD4-IN-4 (0.25-0.5 µM in MDA-MB-231, 1-2.5 µM in KP4) inhibits MDA-MB-231 and KP4 cell invasion[1].
PARP1/BRD4-IN-4 (0.05-0.1 µM in MDA-MB-231, 1-2.5 µM in KP4; 0-48 h) inhibits MDA-MB-231 and KP4 cell migration in the wound healing assay[1].
PARP1/BRD4-IN-4 exhibits extremely high activity in SNU-16 (IC50 0.03 μM) and MDA-MB-468 (IC50 0.06 μM) cells, and the lowest activity in RAW 264.7 cells (IC50 > 50 μM)[1].
PARP1/BRD4-IN-4 (1-10 µM; exposure at 42-62°C for 5 min) directly binds PARP1 and BRD4 in MDA-MB-231 cells, increasing their thermal stability[1].
PARP1/BRD4-IN-4 (1 µM; 3 days) induces DNA damage in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.5 µM) inhibits HRR-related proteins and BRD4/c-Myc signaling in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.25-0.5 µM) reduces BRCA1, CtIP, and BRD4 mRNA levels in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.25-0.5 µM) reduces JUN and CCL2 mRNA levels in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.025-0.05 µM in MDA-MB-231, 0.5-1 µM in KP4; 14 days) inhibits colony formation in MDA-MB-231 and KP4 cells[1].
PARP1/BRD4-IN-4 (0.25-0.5 µM in MDA-MB-231, 1-2.5 µM in KP4) inhibits MDA-MB-231 and KP4 cell invasion[1].
PARP1/BRD4-IN-4 (0.05-0.1 µM in MDA-MB-231, 1-2.5 µM in KP4; 0-48 h) inhibits MDA-MB-231 and KP4 cell migration in the wound healing assay[1].
PARP1/BRD4-IN-4 exhibits extremely high activity in SNU-16 (IC50 0.03 μM) and MDA-MB-468 (IC50 0.06 μM) cells, and the lowest activity in RAW 264.7 cells (IC50 > 50 μM)[1].
Anti-cancer
Apoptosis
Anti-cancer
Cell Cycle Regulation
PARP1/BRD4-IN-4 (0.5-1 µM; 48 h) induces G1 and G2/M phase accumulation in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.5-1 µM) modulates cell cycle regulators in MDA-MB-231 cells, decreasing Cyclin B1/CDK6/Cyclin D1 and increasing P21/P27[1].
PARP1/BRD4-IN-4 (0.5-1 µM) inhibits cJUN and p-cJUN expression in MDA-MB-231 cells[1].
PARP1/BRD4-IN-4 (0.5-1 µM) modulates cell cycle regulators in MDA-MB-231 cells, decreasing Cyclin B1/CDK6/Cyclin D1 and increasing P21/P27[1].
PARP1/BRD4-IN-4 (0.5-1 µM) inhibits cJUN and p-cJUN expression in MDA-MB-231 cells[1].
Anti-cancer
Innate Immunity
PARP1/BRD4-IN-4 (1 µM) blocks MDA-MB-231-induced migration of THP-1 macrophages[1].
Apoptosis
Cell Cycle Regulation
Innate Immunity
PARP1/BRD4-IN-4 (0.5-1 μM; 72 h) reduces RAW 264.7 macrophage invasion under MDA-MB-231 co-culture conditions, whereas 1 μM and direct exposure at 0.5 and 1 μM do not significantly reduce the invasion of THP-1-derived macrophages or RAW 264.7 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Immunofluorescence[1]
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Cell Line:MDA-MB-231 cells
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Concentration:1 µM
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Incubation Time:3 days
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Result:Increased nuclear p-H2A.X levels.
Cell Cycle Analysis[1]
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Cell Line:MDA-MB-231 cells
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Concentration:0.5 and 1 µM
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Incubation Time:48 h
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Result:At 0.5 µM: G1 = 66.6%, S = 6.58%, G2/M = 25.2%.
At 1 µM: G1 = 65.7%, S = 7.18%, G2/M = 25.2%.
Apoptosis Analysis[1]
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Cell Line:MDA-MB-231 cells
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Concentration:10 and 20 µM
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Incubation Time:72 h
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Result:At 10 µM: Q1 = 0.77%, Q2 = 2.33%, Q3 = 88.4%, Q4 = 8.48%.
At 20 µM: Q1 = 0.91%, Q2 = 2.37%, Q3 = 84.8%, Q4 = 11.9%.
Cell Proliferation Assay[1]
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Cell Line:MDA-MB-231 and KP4 cells
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Concentration:0.025 and 0.05 µM (MDA-MB-231); 0.5 and 1 µM (KP4)
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Incubation Time:14 days
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Result:Inhibited colony formation in a dose-dependent manner in both MDA-MB-231 and KP4 cells.
Cell Migration Assay [1]
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Cell Line:MDA-MB-231 and KP4 cells
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Concentration:0.05 and 0.1 µM (MDA-MB-231); 1 and 2.5 µM (KP4)
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Incubation Time:48 h
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Result:Markedly suppressed wound closure/migration in both MDA-MB-231 and KP4 cells.
Cell Invasion Assay[1]
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Cell Line:MDA-MB-231-co-cultured RAW 264.7 macrophages and directly exposed THP-1-derived macrophages/RAW 264.7 cells
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Concentration:0.5 μM and 1 μM (MDA-MB-231 co-culture RAW 264.7 invasion); 0.5 μM and 1 μM (direct THP-1-derived macrophage and RAW 264.7 exposure)
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Incubation Time:72 h
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Result:In MDA-MB-231 co-culture RAW 264.7 invasion assays, at 0.5 μM invasive cells per field were reduced relative to co-culture alone; at 1 μM invasion was not clearly reduced.
In THP-1-derived macrophages and RAW 264.7 cells treated directly, invasive cell counts at 0.5 and 1 μM remained comparable to control.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUCinf | Vdss | Clearance (CL) |
|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 1.62 h | 0.08 h | 7766.82 ng/mL | 2159.37 ng·h/mL | 2161.21 ng·h/mL | 47.71 mL/kg | 463.27 mL/h/kg |
In Vivo
Anti-cancerInnate Immunity
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCG (female, 7 weeks old)[1]
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Dosage:30 mg/kg
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Administration:i.p.; 5 days/week; 31 days
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Result:Markedly reduced tumor volume relative to the control group at 30 mg/kg.
Reduced pulmonary metastatic rate and metastatic count and decreased lung metastatic foci on H&E staining.
In tumor tissues, downregulated the HRR-related proteins CtIP and BRCA1, the BRD4 downstream effectors c-Myc and cJUN, the EMT-related transcription factor ZEB1, and the macrophage markers F4/80 and ARG1.
Related Protocols :
- Annexin V plus membrane-impermeant dye apoptosis staining
- Cell migration
- BrdU Incorporation Assay
- Patient-Derived Orthotopic Xenograft (PDOX)
- Protocol for Cell Cycle
- Colony Formation (Clonogenic) Assay
- Breast Cancer Modeling
- Phagocytosis Functional Assay
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- CRISPR-Cas9 HDR knock-in/precise editing
- Flow cytometric DNA-content cell-cycle staining
- Patient-Derived Xenograft (PDX)
- Tail-Vein Experimental Metastasis Xenograft
- Apoptosis Solutions
- Cell invasion
- Soft Agar Colony Formation Assay
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Genotoxicity/Mutagenicity Study
Chemical Information
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Molecular Weight 850.91
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Formula C47H39FN6O7S
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SMILES
O=C1C2=C(C=CC=C2)C(CC3=CC=C(F)C(C(NCC(C=C4)=CC=C4NC(C(N5)=CC(C(C6=C(OC7=CC=CC=C7)C=CC(CS(=O)(CC)=O)=C6)=CN8C)=C5C8=O)=O)=O)=C3)=NN1
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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.
Purity & Documentation
Select Batch:
Purity:
99.98%
Assay:
99.98%
ee.:
99.98%
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PARP1/BRD4-IN-4 Related Classifications
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