PARP1-IN-58
PARP1-IN-58 is a ROS-responsive prodrug constructed based on a natural stilbene scaffold, and its active parent nucleus 24c acts as a selective PARP-1 inhibitor. PARP1-IN-58 only hydrolyzes to release the active parent compound in the high-ROS microenvironment of tumors; the active parent compound competitively binds to PARP-1 and blocks DNA single-strand damage repair, upregulates intracellular ROS levels, reduces mitochondrial membrane potential, and thereby induces cell cycle arrest and mitochondria-dependent apoptosis. PARP1-IN-58 exerts potent proliferation-inhibiting effects on BRCA-deficient breast cancer cells under simulated tumor oxidative stress conditions, and exhibits tumor growth inhibitory activity in breast cancer xenograft models. PARP1-IN-58 can be used in cancer-related research.
For research use only. We do not sell to patients.
- Formula: C29H32BNO5
- Molecular Weight:485.38
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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
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Biological Activity
Description
IC50 & Target
[1]|
PARP-1 |
Caspase-3 |
Bax |
Bcl-2 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCC1937 | IC50 |
4.49 μM
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Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer HCC1937 cells under normal culture conditions assessed via multi-dose incubation by MTT assay.
Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer HCC1937 cells under normal culture conditions assessed via multi-dose incubation by MTT assay.
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42475630 |
| SUM149PT | IC50 |
3.81 μM
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Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer SUM149PT cells under normal culture conditions assessed via multi-dose incubation by MTT assay.
Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer SUM149PT cells under normal culture conditions assessed via multi-dose incubation by MTT assay.
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42475630 |
| MDA-MB-436 | IC50 |
3.92 μM
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Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer MDA-MB-436 cells under normal culture conditions assessed via multi-dose incubation by MTT assay.
Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer MDA-MB-436 cells under normal culture conditions assessed via multi-dose incubation by MTT assay.
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42475630 |
| HCC1937 | IC50 |
1.42 μM
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Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer HCC1937 cells under H2O2 pretreatment (simulating tumor oxidative stress) assessed via multi-dose incubation by MTT assay.
Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer HCC1937 cells under H2O2 pretreatment (simulating tumor oxidative stress) assessed via multi-dose incubation by MTT assay.
|
42475630 |
| SUM149PT | IC50 |
0.77 μM
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Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer SUM149PT cells under H2O2 pretreatment (simulating tumor oxidative stress) assessed via multi-dose incubation by MTT assay.
Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer SUM149PT cells under H2O2 pretreatment (simulating tumor oxidative stress) assessed via multi-dose incubation by MTT assay.
|
42475630 |
| MDA-MB-436 | IC50 |
0.88 μM
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Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer MDA-MB-436 cells under H2O2 pretreatment (simulating tumor oxidative stress) assessed via multi-dose incubation by MTT assay.
Antiproliferative activity of prodrug P-24c against human BRCA1-deficient breast cancer MDA-MB-436 cells under H2O2 pretreatment (simulating tumor oxidative stress) assessed via multi-dose incubation by MTT assay.
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42475630 |
In Vitro
PARP1-IN-58 (P-24c) releases the active parent nucleus compound 24c in a concentration-dependent manner when exposed to H2O2 in a cell-free system. Compound 24c potently inhibits PARP-1 and exerts selective proliferation-inhibiting effects on a variety of BRCA-deficient tumor cells. It also dose-dependently increases ROS levels in BRCA-deficient breast cancer cells, induces DNA double-strand breaks, and blocks cell colony formation and migration[1].
PARP1-IN-58 exhibits extremely high stability in rat plasma, with > 90% remaining intact after incubation at 37 °C for 24 h; it also shows high stability in rat liver microsomes[1].
PARP1-IN-58 (pretreated with 10 μM H2O2) exhibits ROS-responsive antiproliferative activity in HCC1937, SUM149PT and MDA-MB-436 cells, with IC50 values ranging from 3.81 to 4.49 μM under normal conditions and from 0.77 to 1.42 μM under oxidative stress conditions[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | AUC0-t | AUC0-∞ | Cmax | Tmax | T1/2 |
|---|---|---|---|---|---|---|---|
| Rat[1] | 5 mg/kg | i.v. | 339.77 mg·h/L | 366.76 mg·h/L | 146.21 mg/L | 0.67 h | 6.06 h |
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 (female, nude, subcutaneous xenograft of SUM149PT BRCA1-deficient breast cancer cells)[1]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.p.; once every 2 days; 21 days
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Result:Significantly reduced tumor weight and volume compared to 10 mg/kg niraparib and 10 mg/kg 24c at 5 mg/kg.
Upregulated pro-apoptotic markers Bax, Caspase-3, and Cleaved Caspase-3, and downregulated antiapoptotic BCL-2 at 5 mg/kg, with effects more pronounced than 10 mg/kg niraparib or 24c.
Showed disrupted tumor cell organization and reduced cytoplasmic volume in treated tumors via H&E staining at 5 mg/kg.
Achieved a tumor growth inhibition (TGI) rate of 69.3% at 10 mg/kg, higher than equivalent doses of niraparib and 24c.
Maintained stable body weight at 5 mg/kg.
Showed no significant tissue damage in major organs (heart, liver, spleen, lung, kidney) via H&E staining at 5 mg/kg.
Chemical Information
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Molecular Weight 485.38
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Formula C29H32BNO5
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SMILES
COC1=CC(/C=C/C2=CC=CC(C(N)=O)=C2OCC3=CC=C(C=C3)B4OC(C)(C(C)(O4)C)C)=CC=C1
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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-58 Related Classifications
HY-187473 Related Classifications
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