Topo I/COX-2-IN-2
Topo I/COX-2-IN-2 (Compound W10) is a potent dual-target inhibitor of Topo I and COX-2 with IC50 values of 0.90 μM and 2.31 μM, respectively. Topo I/COX-2-IN-2 induces cancer cell apoptosis through the mitochondrial pathway.
For research use only. We do not sell to patients.
- CAS No.: 2841455-91-0
- Formula: C24H25ClN4O
- Molecular Weight:420.93
-
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]
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
All Topoisomerase Isoforms
More
Biological Activity
|
Topoisomerase I 0.90 μM (IC50) |
COX-2 2.31 μM (IC50) |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| HCT-116 | IC50 |
8.42 μM
Compound: W10
|
Antitumor activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
Antitumor activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
|
[PMID: 35777102] |
| HT-29 | IC50 |
1.48 μM
Compound: W10
|
Antitumor activity against human HT-29 cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
Antitumor activity against human HT-29 cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
|
[PMID: 35777102] |
| LoVo | IC50 |
4.89 μM
Compound: W10
|
Antitumor activity against human LoVo cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
Antitumor activity against human LoVo cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
|
[PMID: 35777102] |
| RKO | IC50 |
2.06 μM
Compound: W10
|
Antitumor activity against human RKO cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
Antitumor activity against human RKO cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
|
[PMID: 35777102] |
| SW480 | IC50 |
7.36 μM
Compound: W10
|
Antitumor activity against human SW480 cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
Antitumor activity against human SW480 cells assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay
|
[PMID: 35777102] |
Topo I/COX-2-IN-2 (Compound W10) (0-30 μM) shows good toxicity against cancer cells[1].
Topo I/COX-2-IN-2 forms an ionic bonding interaction with DA13 of DNA to improve Topo I inhibition[1].
Topo I/COX-2-IN-2 (0-9 μM, 24 h) arrests cell cycle of HT29 and RKO at G1/G0 phase, induces apoptosis in HT29 and RKO cells through the mitochondrial pathway, and inhibits abnormal activation of the NF-κB/IκB pathway. [1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:HT29, RKO, HCT116, LoVo and SW480
-
Concentration:0-30 μM
-
Incubation Time:72 h
-
Result:Showed good toxicity with IC50 values of 1.48 ± 0.08 μM, 2.06 ± 0.01 μM, 4.89 ± 0.36 μM, 8.42 ± 0.22 μM and 7.36 ± 0.64 μM for HT29, RKO, HCT116, LoVo and SW480 cells, respectively.
-
Cell Line:HT29 and RKO
-
Concentration:2, 4 and 8 μM for HT29; 3, 6 and 9 μM for RKO
-
Incubation Time:24 h
-
Result:Blocked the cell cycle in G1/G0 phase in both HT29 and RKO. In HT29 cells, the arresting activity was not obvious for the ratio of G1/G0 phase in high-concentration treatment group increased from 55.20% to 65.17% slightly, while in RKO cells, the ratio of G1/G0 phase obviously increased from 37.57% to 76.99%.
-
Cell Line:HT29 and RKO
-
Concentration:2, 4 and 8 μM for HT29; 3, 6 and 9 μM for RKO
-
Incubation Time:24 h
-
Result:Mainly induced the late apoptosis in HT29 cells and exhibited dual induction of late and early apoptosis in RKO cells.
Induced the production of reactive oxygen species (ROS) burst and significantly reduce the mitochondrial membrane potential.
-
Cell Line:HT29 and RKO
-
Concentration:2, 4 and 8 μM for HT29; 3, 6 and 9 μM for RKO
-
Incubation Time:24 h
-
Result:Induced increased expression of the pro-apoptotic proteins Bax, cytochrome c and apoptotic effector cleaved caspase 3/9, reduced the expression of the inhibitory factor Bcl-2.
The expressions of phosphorylated NF-κB and IκB were significantly decreased.
Topo I/COX-2-IN-2 has acceptable pharmacokinetic properties for intraperitoneal injection and oral administration[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Male BALB/c nude mice weighing 20–25 g, HT29 xenograft model[1]
-
Dosage:15 and 30 mg/kg
-
Administration:Intraperitoneal injection, twice daily for 2 weeks
-
Result:30 mg/kg group immediately slowed down the tumor growth rate after administration, and almost completely prevented tumor growth in the later stage, and its tumor growth inhibition (TGI) was 57.86%. 15 mg/kg group showed 40.67% TGI.
Showed obvious necrosis on tumor tissue.
-
Animal Model:250–280 g male SD rats[1]
-
Dosage:100 mg/kg and 30 mg/kg
-
Administration:Intragastric administration (100 mg/kg) or intraperitoneal injection (30 mg/kg) (Pharmacokinetics Study)
-
Result:Pharmacokinetic data of Topo I/COX-2-IN-2 (W10) in vivoa[1]
Comp. Dose
(mg/kg)Route T1/2(h) Tmax(h) Cmax
(μg/mL)AUC0-t
(μg⋅h/mL)Topo I/COX-2-IN-2 100 p.o. 8.87 ± 1.92 3.67 ± 0.58 2.00 ± 0.41 24.81 ± 5.76 30 i.p. 4.27 ± 0.22 0.28 ± 0.05 1.60 ± 0.34 5.41 ± 0.20
a Topo I/COX-2-IN-2 was administered to 6 SD rats with different administration methods and doses, and the serum concentration was analyzed. The analysis method is the linear trapezoidal PKsolver 2.0 computer program of the non-compartmental model. All the data are from the above 6 rats, and the data are represented by the mean and standard deviation.
Chemical Information
-
CAS No. 2841455-91-0
-
Molecular Weight 420.93
-
Formula C24H25ClN4O
-
SMILES
ClC1=C(C(NC2=CC=CC=C2C(NC3=CC=C(C=C3)N4CCNCC4)=O)=CC=C1)C
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
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)
Topo I/COX-2-IN-2 Related Classifications
HY-150755 Related Classifications
Powered by Bioz