PARP1-IN-44
PARP1-IN-44, an Olaparib (HY-10162) derivative, is an orally active PARP1 inhibitor (IC50 = 0.6 nM), and also inhibits PARP2 (IC50 = 1.0 nM) and PARP7 (IC50 = 7.5 nM). PARP1-IN-44 has selective antiproliferative activity against BRCA-deficient cancer cells with minimal toxicity to normal cells. PARP1-IN-44 induces G2/M phase arrest, promotes apoptosis, elevates ROS levels, disrupts mitochondrial membrane potential. PARP1-IN-44 suppresses PARylation while increasing γH2AX accumulation. PARP1-IN-44 activates the cGAS-STING pathway, upregulating IFN-β and CXCL10 expression. PARP1-IN-44 enhancing CD8+ T cell infiltration in a CT26 tumor mouse model, demonstrating robust in vivo antitumor efficacy.
For research use only. We do not sell to patients.
- Formula: C27H22F2N4O4S
- Molecular Weight:536.55
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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
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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PARP1 0.6 nM (IC50) |
PARP2 1 nM (IC50) |
PARP7 7.5 nM (IC50) |
PARP3 12.5 nM (IC50) |
PARP5A 20.5 nM (IC50) |
PARP5B 38.1 nM (IC50) |
PARP1-IN-44 (Compound B3) (3.63-100 μM, 5 days) has anti-proliferative activity against a panel of tumor cells, with IC50s of 9.70 μM HCT-15), 5.80 μM (HCC1937), 18.06 μM (HepG2), 16.48 μM (MCF7), and 9.88 μM (Capan-1), 12.48μM (CT26), and displays an excellent safety profile, with IC50 values greater than 100 μM against the non-cancerous NCM460 and GES-1 cell lines[1].
PARP1-IN-44 (2.5-10 μM, 48 h) induces apoptosis and cell cycle arrest in HCC1937 cells[1].
PARP1-IN-44 (2.5-10 μM, 24 h) inhibits PARP1 mediated H2O2-induced DNA damage repair in HCC1937 cells[1].
PARP1-IN-44 (2.5-10 μM, 24 h) induces ROS accumulation (detected with the DCFH-DA probe (HY-D0940)) and mitochondrial depolarization (assessed by JC-1 (HY-15534) staining) in HCC1937 cells[1].
PARP1-IN-44 (0.25-2 μM, 72 h) restores the innate immune response in CT26 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCC1937 cells
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Concentration:2.5, 5, 10 μM
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Incubation Time:48 h
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Result:Induced apoptosis in a concentration dependent manner, with apoptosis rates of 37.14 % and 62.64 % at concentrations of 5 μM and 10 μM.
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Cell Line:CT26 cells
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Concentration:0.25, 0.5, 1 and 2 μM
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Incubation Time:72 h
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Result:Increased in the expression of immune-related genes (IFN-β and CXCL10).
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Cell Line:H2O2 (600 μM, 30 min)-induced HCC1937 cells
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Concentration:1 μM
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Incubation Time:72 h
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Result:Decreased fluorescence intensity of PAR (green) compared to the H2O2-induced group.
Increased γH2AX (green) fluorescence intensity in a concentration dependent manner.
| Species | Dose | Route | T1/2 | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ | Cmax | Vz | CL |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2.5 mg/kg | i.p. | 5.54 h | 460.787 ng·h/mL | 486.47 ng·h/mL | 4.27 h | 5.74 h | 147.69 L/kg | 328.51 L/kg | 41.16 L/h/kg |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Six-week-old female BALB/c mice subcutaneously inoculated with CT26 cells in the axillary region[1].
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Dosage:30 mg/kg and 50 mg/kg
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Administration:Oral gavage, once daily for 14 days
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Result:Significantly reduced both tumor volume and weight, with the 30 mg/kg dose group exhibiting comparable tumor inhibition efficacy to RBN-2397 (HY-136174) (30 mg/kg, p.o.).
Demonstrated remarkable antitumor effects with approximately 5-fold reduction in average tumor volume and approximately 943 mg decrease in tumor weight at 50 mg/kg dose group compared to the control group.
Had no significant differences in body weight changes.
Displayed pronounced morphological changes (H&E staining): chromatin condensation, nuclear fragmentation, nuclear envelope rupture, increased and enlarged cytoplasmic vacuolation, loose cellular arrangement, and reduced intercellular connections.
Promoted the infiltration of CD8+ T cells in the tumor microenvironment.
Chemical Information
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Molecular Weight 536.55
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Formula C27H22F2N4O4S
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SMILES
O=C(NC1(C2)CC2(NS(=O)(C3=CC=C(F)C=C3)=O)C1)C4=CC(CC5=NNC(C6=C5C=CC=C6)=O)=CC=C4F
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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)
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