DDO3602
DDO3602 is a PARP1 HSPTAC (HSP90-mediated proteolysis-targeting chimera) degrader, with a DC50 of 490.3 nM against PARP1; its Kd values for PARP1 and HSP90 are 66.5 nM and 1.64 nM, respectively. DDO3602 induces the formation of an unnatural PARP1-HSP90 ternary complex, recruits E3 ubiquitin ligase, and promotes PARP1 degradation via the ubiquitin-proteasome pathway. DDO3602 induces G2/M cell cycle arrest, DNA damage, inhibits cell migration, and exhibits antiproliferative activity in breast cancer cells. DDO3602 can be used in breast cancer-related research.
(Pink: PARP1 ligand (HY-75706); Blue: HSP90 ligand (HY-179203); Black: linker (HY-W015300)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C51H58FN7O7
- Peso molecular:900.05
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Almacenamiento:
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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Actividad biológica
Descripciòn
IC50 & Target
[1]|
Hsp90TACs |
PARP1 490.3 nM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MCF7 | DC50 |
490.3 nM
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PARP1 protein degradation in human MCF-7 breast cancer cells assessed via Western blot with GAPDH as loading control after 9 h incubation.
PARP1 protein degradation in human MCF-7 breast cancer cells assessed via Western blot with GAPDH as loading control after 9 h incubation.
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41004278 |
| MCF7 | IC50 |
0.189 μM
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Inhibition of cell viability in human MCF-7 breast cancer cells measured via CCK-8 assay after 72 h incubation.
Inhibition of cell viability in human MCF-7 breast cancer cells measured via CCK-8 assay after 72 h incubation.
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41004278 |
| MCF-10A | IC50 |
0.744 μM
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Inhibition of cell viability in human MCF-10A normal breast epithelial cells measured via CCK-8 assay after 72 h incubation.
Inhibition of cell viability in human MCF-10A normal breast epithelial cells measured via CCK-8 assay after 72 h incubation.
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41004278 |
In Vitro
DDO3602 (0-3 μM; 9 h) degrades PARP1 in human breast cancer MCF-7 cells in a dose-dependent manner, with a DC50 of 490.3 nM, and the degradation rate reaches 70.6% after incubation at 1 μM for 9 h[1].
DDO3602 (1 μM; 0-24 h) induces significant degradation of PARP1 in human breast cancer MCF-7 cells within 3 h, with nearly complete depletion achieved by 9 h[1].
DDO3602 (1 μM; 0-24 h) degrades the pre-existing PARP1 protein in MCF-7 human breast cancer cells, rather than inhibiting its synthesis[1].
DDO3602 (0-1 μM) exerts a stronger inhibitory effect on colony formation in human breast cancer MCF-7 cells than in normal mammary epithelial MCF-10A cells[1].
DDO3602 (0-10 μM; 72 h) inhibits the viability of MCF-7 human breast cancer cells with an IC50 of 0.189 μM; its potency is approximately 4-fold higher than that against MCF-10A normal mammary epithelial cells (IC50 = 0.744 μM) after 72 h of treatment[1].
DDO3602 (0.5-1 μM; 24 h) induces dose-dependent G2/M cell cycle arrest in human breast cancer MCF-7 cells[1].
DDO3602 (1 μM; 24 h) induces significant DNA double-strand break formation in MCF-7 human breast cancer cells (detected by γ-H2A.X accumulation)[1].
DDO3602 (0.1-1 μM; 48 h) significantly inhibits the migration of MCF-7 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7 human breast cancer cells
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Concentration:0, 0.1, 0.2, 0.3, 0.4, 0.6, 0.8, 1, 1.5, 2, 2.5 and 3 μM
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Incubation Time:9 h
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Result:Reduced PARP1 protein levels in a dose-dependent manner, achieving a degradation half-maximal effective concentration (DC50) of 490.3 nM, and causing 70.6% PARP1 degradation at 1 μM.
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Cell Line:MCF-7 human breast cancer cells
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Concentration:1 μM
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Incubation Time:0, 3, 6, 9, 12 and 24 h
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Result:Significantly reduced PARP1 protein levels within 3 h, with near-complete depletion of PARP1 observed at 9 h.
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Cell Line:MCF-7 human breast cancer cells
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Concentration:0.5 and 1 μM
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Incubation Time:24 h
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Result:Induced G2/M phase cell cycle arrest in a dose-dependent manner; 0.5 μM increased the percentage of cells in G2/M phase to 59.0%, and 1 μM increased this percentage to 62.7%, compared to 24.9% in control cells.
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Cell Line:MCF-7 human breast cancer cells
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Concentration:1 μM
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Incubation Time:24 h
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Result:Induced a greater accumulation of γ-H2A.X than an equivalent concentration of Olaparib (HY-10162), indicating stronger induction of DNA damage.
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Cell Line:MCF-7 human breast cancer cells
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Concentration:0.1 and 1 μM
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Incubation Time:48 h
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Result:Diminished wound healing capacity of MCF-7 cells more effectively than an equivalent concentration of Olaparib, indicating stronger inhibition of cell migration.
Parmacokinetics
| Species | Dose | Route | Cmax | AUC0-t | T1/2 |
|---|---|---|---|---|---|
| Rat[1] | 10 mg/kg | i.p. | 2370.00 ng/mL | 16261.40 ng·h/mL | 2.78 h |
In Vivo
DDO3602 (20 mg/kg; i.v.; single dose) exhibits tumor-targeted pharmacokinetics in MCF-7 xenograft mice, with significantly higher accumulation in tumor tissue than normal tissues following a single 20 mg/kg intravenous dose[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Immunocompromised mice (MCF-7 xenograft model)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.p.; every other day; 21 days
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Result:Suppressed tumor growth in a dose-dependent manner.
Achieved significant tumor regression at the 20 mg/kg dose.
Reduced mean tumor weights significantly compared to the control group at study endpoint.
Caused no significant body weight loss or organ toxicity via H&E staining of heart, liver, spleen, lung, and kidney tissues.
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Animal Model:Immunocompromised mice (MCF-7 xenograft model)[1]
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Dosage:20 mg/kg
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Administration:i.v.; single dose
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Result:Reached a concentration in tumor tissue 13-fold higher than in spleen and over 33-fold higher than in liver, kidney, lung, heart, plasma, muscle, and intestinal tissues at 12 h post-dose.
Maintained significantly higher concentrations in tumor tissue than all other tissues at 24 h post-dose.
Chemical Information
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Peso molecular 900.05
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Fòrmula C51H58FN7O7
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SMILES
CC(C1=C(C=C(C(C(N2CC3=C(C2)C=CC(CN4CCN(CC4)C(CCCCCCC(N5CCN(C(C6=CC(CC7=NNC(C8=CC=CC=C87)=O)=CC=C6F)=O)CC5)=O)=O)=C3)=O)=C1)O)O)C
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DDO3602 Related Classifications
HY-178496 Related Classifications
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