PARP1-IN-40
PARP1-IN-40 is a highly selectively and orally active PARP1 inhibitor (IC50: 0.19 nM for PARP1, 26 nM for PARP2). PARP1-IN-40 kills tumor cells by inhibiting PARP1, leading to accumulation of DNA damage. PARP1-IN-40 has high antitumor activity against BRCA mutant MDA-MB-436 cells. PARP1-IN-40 can be used in combination with chemotherapy for cancer-related research.
For research use only. We do not sell to patients.
- Formula: C25H24FN5O2
- Molecular Weight:445.49
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
PARP1-IN-40 (Compound (S)-G9) (1-100 nM, 3 days) blocks the MDA-MB-436 cell cycle at the G2/M phase and inhibits proliferation[1].
PARP1-IN-40 (0.1-1000 nM, 3 days) induces DNA damage and double-strand breaks in MDA-MB-436 cells[1].
PARP1-IN-40 (0.1-10000 nM, 1 h) was almost inactive in PARP1-KO cells in A549 cells (IC50 > 9.8 μM), proving that its action is completely dependent on PARP1 and its inhibitory activity on PARP2 is extremely weak, thus avoiding the toxicity risk of traditional PARPi[1].
PARP1-IN-40 (0.1-10000 nM, 1 h) efficiently captures PARP1-DNA complexes (EC50 = 1.9 nM), while capturing PARP2 requires a thousand-fold concentration, making it a PARP1 selective capture agent[1].
PARP1-IN-40 (0.1-20000 nM, 10 days) selectively kills BRCA mutant cells, confirming that its synthetic lethality mechanism depends on homologous recombination deficiency[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-436 cells
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Concentration:1 nM, 10 nM, 100 nM
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Incubation Time:3 days
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Result:Reduced the number of cells in S phase and significantly increased the number of cells in G2/M phase in a dose-dependent manner.
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Cell Line:MDA-MB-436 cells, DLD-1 BRCA2-KO cells, DLD-1 WT cells
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Concentration:0.1 nM, 1 nM, 10 nM, 100 nM (MDA-MB-436 cells, DLD-1 BRCA2-KO cells); 2.5 μM, 5 μM, 10 μM, 20 μM (DLD-1 WT cells)
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Incubation Time:10 days
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Result:Completely inhibited clone formation in BRCA1 mutant (MDA-MB-436) and BRCA2 null (DLD-1 KO) cells at low concentrations, and showed no toxicity to BRCA wild-type cells (DLD-1 WT) even at high concentrations.
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Cell Line:MDA-MB-436 cells
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Concentration:0.1 nM, 1 nM, 10 nM, 100 nM, 1000 nM
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Incubation Time:3 days
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Result:Significantly increased the number of γH2AX foci.
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Cell Line:MDA-MB-436 cells
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Concentration:0.1 nM, 1 nM, 10 nM, 100 nM, 1000 nM
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Incubation Time:3 days
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Result:Increased the expression of γH2AX.
| Species | Dose | Route | Tmax | Cmax | AUC0-t |
|---|---|---|---|---|---|
| Mice | 1 mg/kg | i.v. | 0.008 h | 1.2E4 ng/mL | 2.4E5 ng·h/mL |
| Mice | 1 mg/kg | p.o. | 3.01 h | 6.6E3 ng/mL | 2.4E5 ng·h/mL |
| Mice | 10 mg/kg | i.v. | 0.08 h | 4.9E4 ng/mL | 1.5E6 ng·h/mL |
| Mice | 10 mg/kg | p.o. | 2 h | 3.8E4 ng/mL | 1.5E6 ng·h/mL |
| Mice | 3 mg/kg | i.v. | 0.08 h | 1.8E4 ng/mL | 7.3E5 ng·h/mL |
| Mice | 3 mg/kg | p.o. | 2 h | 2.0E4 ng/mL | 9.3E5 ng·h/mL |
| Rat | 2.5 mg/kg | i.v. | 0.08 h | 5.3E3 ng/mL | 7.0E4 ng·h/mL |
| Rat | 2.5 mg/kg | p.o. | 5 h | 3.2E3 ng/mL | 6.2E4 ng·h/mL |
PARP1-IN-40 (Compound (S)-G9) (0.3-3 mg/kg, p.o, for 27 days) potently inhibits the growth of BRCA mutant tumors without significant toxicity in the MDA-MB-231 xenograft mice model[1].
PARP1-IN-40 (1-3 mg/kg, p.o, for 14 days) has synergistic effect with chemotherapy in the HCT116 xenograft mice model[1].
PARP1-IN-40 (30-300 mg/kg, p.o, once dose; 30-100 mg/kg, p.o, for 14 days) is highly safe in the BALB/C nude mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:MDA-MB-231 xenograft model established in nude mice[1]
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Dosage:0.3 mg/kg, 1 mg/kg, 3 mg/kg
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Administration:Oral administration (p.o.), at the corresponding doses for 27 days
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Result:Had TGI of 80 % at a dose of 0.3 mg/kg and 94 % at 3 mg/kg, with stable mouse body weight.
Blocked DNA repair in tumor tissues by selectively inhibiting PARP1, leading to the accumulation of γH2AX-mediated DNA damage, which in turn downregulated Ki67 to inhibit proliferation and drive anti-tumor efficacy.
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Animal Model:HCT116 xenograft model established in nude mice[1]
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Dosage:1 mg/kg or 3mg/kg + liposomal Irinotecan (HY-16562) (2 mg/kg)
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Administration:PARP1-IN-40: Oral administration (p.o.), at the corresponding doses for 14 days; liposomal Irinotecan: Intravenous injection (i.v.), twice weekly for 14 days.
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Result:Had a TGI of 80 % at 1 mg/kg combined with chemotherapy and 85 % at 3 mg/kg.
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Animal Model:Famale and male BALB/C nude mice[1]
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Dosage:30 mg/kg, 100 mg/kg, 300 mg/kg
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Administration:Oral administration (p.o.) at 30 mg/kg and 100 mg/kg for 14 days; Oral administration (p.o.) at 30 mg/kg, 100 mg/kg and 300mg/kg once dose
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Result:Did not cause death or significant weight changes in mice, and the histology of the heart, liver, spleen, lung, and kidney was normal.
Had no significant organ toxicity even at doses far higher than the therapeutic dose, and had excellent oral safety.
Chemical Information
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Molecular Weight 445.49
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Formula C25H24FN5O2
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SMILES
CNC(C1=CC=C(C=N1)C2=CCN(C[C@H]2C)CC3=CC4=C(N5C=CC(F)=C5C(N4)=O)C=C3)=O
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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-IN-40 Related Classifications
HY-174442 Related Classifications
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