PARP1/2/TNKS1/2-IN-1
Based on 1 Customer Validation
PARP1/2/TNKS1/2-IN-1 is a potent and selective dual PARP-1/2 and TNKS1/2 inhibitor with IC50 values of 0.25 nM, 1.2 nM, 13.5 nM and 4.15 nM for PARP-1, PARP-2, TNKS1 and TNKS2, respectively. PARP1/2/TNKS1/2-IN-1 suppresses Wnt/β-catenin signaling, decreases pADPr and BRCA1 expression, induces DNA damage, promotes apoptosis, and arrests the cell cycle at the G2/M phase. PARP1/2/TNKS1/2-IN-1 can be used for the study of on colorectal cancer and triple-negative breast cancer.
For research use only. We do not sell to patients.
- Purity: 98.66%
- CAS No.: 2243453-32-7
- Formula: C35H31FN6O5
- Molecular Weight:634.66
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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PARP-1 0.25 nM (IC50) |
PARP-2 1.2 nM (IC50) |
TNKS2 4.15 nM (IC50) |
TNKS1 13.5 nM (IC50) |
PARP-7 15 nM (IC50) |
PARP-10 140 nM (IC50) |
PARP-12 371 nM (IC50) |
PARP-14 1369 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| AML12 | CC50 |
117.47 μM
Compound: I-9
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Cytotoxicity against mouse AML12 cells assessed as reduction in cell viability incubated for 7 days by MTT assay
Cytotoxicity against mouse AML12 cells assessed as reduction in cell viability incubated for 7 days by MTT assay
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[PMID: 35504210] |
| HCT-116 | IC50 |
0.75 μM
Compound: I-9
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Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay
Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay
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[PMID: 35504210] |
| MDA-MB-231 | IC50 |
0.87 μM
Compound: I-9
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Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay
Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay
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[PMID: 35504210] |
| MDA-MB-468 | IC50 |
0.09 μM
Compound: I-9
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Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay
Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth incubated for 7 days by MTT assay
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[PMID: 35504210] |
PARP1/2/TNKS1/2-IN-1 (compound I-9) inhibits PARP-1, PARP-2, TNKS1 and TNKS2 with IC50 values of 0.25 nM, 1.2 nM, 13.5 nM and 4.15 nM, respectively; it also inhibits PARP-7, PARP-10, PARP-12 and PARP-14 with IC50 values of 15.0 nM, 140.0 nM, 371.0 nM and 1369.0 nM, respectively, and shows weak or no inhibitory activity against 208 tested kinases at 1 μM[1].
PARP1/2/TNKS1/2-IN-1 (0.01-10 μM; 7 days) inhibits MDA-MB-231, HCT116 and MDA-MB-468 cancer cell proliferation, with IC50 values of 0.87 μM, 0.75 μM and 0.09 μM, respectively[1].
PARP1/2/TNKS1/2-IN-1 shows low cytotoxicity in AML12 cells, with a CC50 of 117.47 μM[1].
PARP1/2/TNKS1/2-IN-1 (10 μM) modulates PARP- and Wnt/β-catenin-related signaling in HCT116 cells by decreasing pADPr, active β-catenin, total β-catenin, cyclin D1 and BRCA1 expression, and increasing axin2 expression[1].
PARP1/2/TNKS1/2-IN-1 (1 μM; 72 h) reduces RAD51 foci formation and increases γH2AX nuclear foci in HCT116 cells[1].
PARP1/2/TNKS1/2-IN-1 (1, 5 μM; 3 days) promotes apoptosis and arrests the cell cycle at the G2/M phase in HCT116 cells[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, HCT116, MDA-MB-468
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Concentration:0.01-10 μM
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Incubation Time:7 days
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Result:Inhibited MDA-MB-231, HCT116, MDA-MB-468 cell proliferation, with IC50 values of 0.87 μM, 0.75 μM and 0.09 μM, respectively.
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Cell Line:HCT116
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Concentration:1 μM
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Incubation Time:72 h
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Result:Reduced RAD51 foci formation and impaired homologous recombination repair efficiency.
Increased nuclear γH2AX foci, indicating enhanced DNA double-strand damage.
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Cell Line:HCT116
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Concentration:1, 5 μM
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Incubation Time:3 days
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Result:Promoted HCT116 cell apoptosis. At 5 μM, induced more apoptotic cells than 5 μM Olaparib (HY-10162) and 5 μM E7449 (HY-12418).
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Cell Line:HCT116
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Concentration:1, 5 μM
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Incubation Time:3 days
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Result:Promoted the G1/S transition and arrested the cell cycle at the G2/M phase at 1 μM and 5 μM.
| Species | Dose | Route | T1/2 | Tmax | Cmax | C0 | AUC0-t | AUC0-∞ | Vz | CL | MRT0-t | MRT0-∞ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 1.73 h | 0.083 h | 28.7 ng/mL | 389.0 ng/mL | 175.6 ng·h/mL | 184.1 ng·h/mL | 13571 mL/kg | 5440 mL/h/kg | 0.77 h | 1.13 h |
PARP1/2/TNKS1/2-IN-1 (500 mg/kg; i.p.; single dose) shows no obvious acute toxicity or intestinal toxicity in Sprague-Dawley rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice, 5-6 weeks old, 18-20 g, subcutaneously inoculated with 5 × 106 HCT116 cells on the right flank[1]
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Dosage:25, 50, 100 mg/kg
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Administration:Intraperitoneal injection (i.p.); once daily; for 28 days
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Result:Suppressed HCT116 xenograft tumor growth in a dose-dependent manner.
Achieved a TGI of 31.73% at 25 mg/k.
Achieved significant antitumor activity at 100 mg/kg, with a TGI of 51.74%.
Reduced tumor volume and tumor weight compared with the control group.
Did not cause remarkable toxicity, side effects or obvious body weight decrease during the 28-day dosing period.
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Animal Model:Sprague-Dawley rat acute toxicity and intestinal toxicity model, half male and half female[1]
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Dosage:500 mg/kg
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Administration:Intraperitoneal injection (i.p.); single dose
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Result:Caused no rat death after a single-dose administration.
Did not induce significant body weight loss from day 0 to day 7.
Showed no obvious intestinal toxicity in the duodenum, jejunum, ileum and colon according to histopathological analysis.
Chemical Information
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CAS No. 2243453-32-7
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Appearance Solid
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Molecular Weight 634.66
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Formula C35H31FN6O5
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Color White to light yellow
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SMILES
O=C(N1CCN(C(C2=CC(CC3=NNC(C4=C3C=CC=C4)=O)=CC=C2F)=O)CC1)NC5=CC=C(C(NC6=CC=C(OC)C=C6)=O)C=C5
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Purity & Documentation
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Data Sheet (276 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PARP1/2/TNKS1/2-IN-1 Related Classifications
HY-146336 Related Classifications
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- PARP1/2/TNKS1/2-IN-1
- 2243453-32-7
- PARP
- Apoptosis
- Wnt
- β-catenin
- PARP-1 inhibitor
- PARP-2 inhibitor
- TNKS1 inhibitor
- TNKS2 inhibitor
- dual inhibitor
- selective
- Wnt/β-catenin signaling pathway
- pADPr
- axin2
- cyclin D1
- BRCA1
- RAD51
- γH2AX
- apoptosis
- cell cycle arrest
- DNA damage
- MDA-MB-231
- HCT116
- MDA-MB-468
- AML12
- HCT116 xenograft model
- colorectal cancer
- triple-negative breast cancer
- Inhibitor
- inhibitor
- inhibit