Topo I/COX-2-IN-2 (Compound W10) 是一种有效的Topo I和COX-2的双靶点抑制剂，IC50值分别为 0.90 μM 和 2.31 μM。Topo I/COX-2-IN-2 通过线粒体途径诱导癌细胞凋亡（apoptosis）。
| 生物活性 | Topo I/COX-2-IN-2 (Compound W10) is a potent dual-target inhibitor ofTopo IandCOX-2withIC50values of 0.90 μM and 2.31 μM, respectively. Topo I/COX-2-IN-2 inducescancercellapoptosisthrough the mitochondrial pathway[1]. |
| IC50& Target | Topoisomerase I 0.90 μM (IC50) | COX-2 2.31 μM (IC50) |
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体外研究
(In Vitro) | 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].
Cell Proliferation Assay[1] | Cell Line: | HT29, RKO, HCT116, LoVo and SW480 | | Concentration: | 0-30 μM | | Incubation Time: | 72 h | | Result: | Showed good toxicity with IC50values 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 Cycle Analysis[1] | 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%. |
Apoptosis Analysis[1] | 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. |
Western Blot Analysis[1] | 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. |
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体内研究
(In Vivo) | Topo I/COX-2-IN-2 (Compound W10) (15 and 30 mg/kg; i.p.; b.i.d for 2 weeks) inhibits tumor growth and shows obvious necrosis on tumor tissue[1].
Topo I/COX-2-IN-2 has acceptable pharmacokinetic properties for intraperitoneal injection and oral administration[1].
| 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 |
aTopo 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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