PARP1/PRMT5-IN-1
PARP1/PRMT5-IN-1 is an inhibitor of PARP1 and PRMT5, with an IC50 of 0.60 nM against PARP1 and an IC50 of 4.67 nM against PRMT5. PARP1/PRMT5-IN-1 downregulates the homologous recombination (HR)-associated factors BRCA1, BRCA2, and RAD51, thereby suppressing homologous recombination function. PARP1/PRMT5-IN-1 induces the accumulation of DNA double-strand breaks. PARP1/PRMT5-IN-1 triggers apoptosis. PARP1/PRMT5-IN-1 is applicable for breast cancer research.
For research use only. We do not sell to patients.
- CAS No.: 3133817-84-9
- Formula: C41H43FN8O4
- Molecular Weight:730.83
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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All Histone Methyltransferase Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
PARP1 0.60 nM (IC50) |
PRMT5 4.67 nM (IC50) |
BRCA1 |
BRCA2 |
RAD51 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| MDA-MB-436 | IC50 |
0.76 μM
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Antiproliferative activity against human MDA-MB-436 breast cancer cells assessed by MTT assay after 7 days of incubation.
Antiproliferative activity against human MDA-MB-436 breast cancer cells assessed by MTT assay after 7 days of incubation.
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42607456 |
| MDA-MB-468 | IC50 |
0.48 μM
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Antiproliferative activity against human MDA-MB-468 breast cancer cells assessed by MTT assay after 7 days of incubation.
Antiproliferative activity against human MDA-MB-468 breast cancer cells assessed by MTT assay after 7 days of incubation.
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42607456 |
| MDA-MB-231 | IC50 |
0.29 μM
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Antiproliferative activity against human MDA-MB-231 breast cancer cells assessed by MTT assay after 7 days of incubation.
Antiproliferative activity against human MDA-MB-231 breast cancer cells assessed by MTT assay after 7 days of incubation.
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42607456 |
| MCF7 | IC50 |
0.27 μM
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Antiproliferative activity against human MCF-7 breast cancer cells assessed by MTT assay after 7 days of incubation.
Antiproliferative activity against human MCF-7 breast cancer cells assessed by MTT assay after 7 days of incubation.
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42607456 |
In Vitro
PARP1/PRMT5-IN-1 exerts potent dual nanomolar inhibitory activity against purified recombinant PARP1 and PRMT5 enzymes[1].
PARP1/PRMT5-IN-1 exhibits high selectivity for PARP1/PARP2 and PRMT5 over closely related PARP and PRMT family isoforms[1].
PARP1/PRMT5-IN-1 (30 μM; 4 h) directly and potently binds to both endogenous PARP1 and PRMT5 proteins in intact MDA-MB-231 breast cancer cells[1].
PARP1/PRMT5-IN-1 (0.3-3 μM; 5 days) effectively suppresses the catalytic activity of both PARP1 and PRMT5 in living MDA-MB-231 cells without affecting total protein expression levels of the two targets, and does not interfere with type I PRMT enzyme activity[1].
PARP1/PRMT5-IN-1 (compound 8I) (7 days) exerts potent antiproliferative effects independent of BRCA mutational status across both BRCA-mutant MDA-MB-436 and BRCA wild-type MDA-MB-468, MDA-MB-231, and MCF-7 human breast cancer cell lines[1].
PARP1/PRMT5-IN-1 (0.3-1 μM; 12 days) exerts superior long-term antiproliferative and colony-suppressive effects in BRCA wild-type MDA-MB-231 breast cancer cells relative to single-agent PARP1 or PRMT5 inhibitors[1].
PARP1/PRMT5-IN-1 (1-3 μM; 5 days) induces prominent double-strand DNA damage and suppresses homologous recombination via reduction of RAD51 foci formation in MDA-MB-231 breast cancer cells[1].
PARP1/PRMT5-IN-1 (1-3 μM; 5 days) induces higher levels of accumulated DNA break damage in MDA-MB-231 breast cancer cells than treatment with single-agent PARP1 inhibition, single-agent PRMT5 inhibition, or their combination[1].
PARP1/PRMT5-IN-1 (3 μM; 5 days) induces synergistic dual S and G2/M phase cell cycle arrest in MDA-MB-231 breast cancer cells[1].
PARP1/PRMT5-IN-1 (3 μM; 5 days) induces robust apoptotic cell death in MDA-MB-231 breast cancer cells that is greater than the apoptosis induced by single-agent PARP1 or PRMT5 inhibition or their combination[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 breast cancer cells
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Concentration:30 μM
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Incubation Time:4 h
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Result:Directly and potently binded to endogenous PARP1 and PRMT5 proteins in intact MDA-MB-231 breast cancer cells.
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Cell Line:MDA-MB-231 human breast cancer cells
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Concentration:0.3 μM; 1 μM; 3 μM
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Incubation Time:5 days
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Result:Did not alter total PARP1 or PRMT5 protein expression levels.
Effectively reduced the cellular levels of poly ADP-ribose (p-ADPr), histone H4 symmetric dimethylarginine at residue 3 (H4R3me2s), and global symmetric dimethylarginine (SDMA).
Did not cause any change in the levels of asymmetric dimethylarginine (ADMA).
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Cell Line:MDA-MB-231 human breast cancer cells
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Concentration:3 μM
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Incubation Time:5 days
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Result:Led to significant concurrent accumulation of cells in both S phase and G2/M phase, producing a synergistic cell cycle arrest effect that combined the separate S phase arrest induced by Olaparib (HY-10162) and G2/M phase arrest induced by GSK3326595 (HY-101563).
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Cell Line:MDA-MB-231 human breast cancer cells
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Concentration:3 μM
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Incubation Time:5 days
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Result:Effectively induced apoptosis in MDA-MB-231 cells, producing an apoptosis rate of 20.15%.
This apoptosis rate was higher than the rates of 6.09% achieved by Olaparib alone, 7.43% achieved by GSK3326595 alone, and 10.48% achieved by the combination of the two single agents.
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Cell Line:MDA-MB-231 human breast cancer cells
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Concentration:1 μM; 3 μM
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Incubation Time:5 days
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Result:Significantly induced the formation of nuclear γH2AX foci (a marker of DNA double-strand breaks) while markedly decreasing the number of nuclear RAD51 foci (a marker of active homologous recombination repair), compared to treatment with Olaparib or GSK3326595 alone.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/C nude mice (Female, 4-5 weeks old)[1]
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Dosage:40 mg/kg; 80 mg/kg
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Administration:i.p.; once daily; 27 consecutive days
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Result:Achieved tumor growth inhibition (TGI) rate of 44% at 40 mg/kg/day.
Achieved tumor growth inhibition (TGI) rate of 79% at 80 mg/kg/day.
Showed no obvious body weight loss across all groups.
Upregulated the expression of DNA damage marker γH2AX in excised tumors.
Downregulated the proliferation marker Ki-67 in excised tumors.
Did not induce remarkable alterations in the cellular morphology or tissue structure of the heart, liver, spleen, lungs, and kidneys after 27 days of continuous administration.
Chemical Information
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CAS No. 3133817-84-9
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Molecular Weight 730.83
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Formula C41H43FN8O4
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SMILES
O=C1NN=C(CC2=CC(C(N3CCC4(CC(NC5=NC=NC(C(NC[C@H](O)CN6CCC(C=CC=C7)=C7C6)=O)=C5)C4)CC3)=O)=C(F)C=C2)C8=CC=CC=C81
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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
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PARP1/PRMT5-IN-1 Related Classifications
HY-189242 Related Classifications
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