topoisomerase IIα

TopoisomeraseIIα-IN-10 (Compound 13r) is a topoisomerase IIα inhibitor that binds to the active site of DNA when complexed with topoisomerase IIα. This binding is stabilized through interactions with DNA base pairs and amino acid residues. By intercalating into DNA, TopoisomeraseIIα-IN-10 induces apoptosis and disrupts the mitochondrial membrane potential in HCT116 cells, effectively inhibiting their growth with an IC50 of 4.37 μM. It is applicable for cancer research studies.

Topoisomerase IIα-IN-4 (F2) is a non-intercalative ATP-competitive inhibitor of human DNA topoisomerase II, selectively inhibiting TopoIIα with an IC50 value of 3.8 μM and TopoIIβ with an IC50 value of 10.1 μM. It induces apoptosis and arrests the cell cycle in HepG2 cells, demonstrating strong antitumor effects against various human cancer cell lines, thereby highlighting its significance for cancer research [1].

Topoisomerase IIα-IN-1 (compound 2) is a potent TopoIIα inhibitor and DNA-binding ligand, exhibiting significant anti-proliferative effects on human cancer cell lines.

Topoisomerase IIα-IN-2 (compound 5) is a potent inhibitor of the topoisomerase TopoIIα and a DNA-binding ligand. It exhibits high anti-proliferative activity in human cancer cell lines, arrests the cell cycle in the G2 M phase, and significantly induces DNA damage.

Topoisomerase IIα-IN-3 is a DNA-inserting topoisomerase-Iiα inhibitor that blocks the cell cycle in G0 G1 phase and induces apoptosis.

Topoisomerase IIα-IN-8 (compound 15) serves as a modest inhibitor of human DNA topoisomerase IIα (htIIα), exhibiting an inhibitory concentration (IC50) of 462 ± 38.0 μM [1].

Proscillaridin A is a natural product.It is a potent poison of topoisomerase I II activity with IC50 values of 30 nM and 100 nM, respectively.

AuL1 is a topoisomerase IIα (Top II) inhibitor with DNA intercalating properties. It exhibits cytotoxic effects on tumor cells, making it a potential subject for anticancer agent research.

TAS-103 is a dual inhibitor of DNA topoisomerase I II, utilized in cancer research.

ARN-21934 is a potent, highly selective, blood-brain barrier (BBB) penetrant inhibitor for human topoisomerase II α over β. It inhibits DNA relaxation with an IC50 of 2 μM, compared to 120 μM for Etoposide. ARN-21934 exhibits favorable in vivo pharmacokinetic properties and shows promise in anticancer research, displaying affinity for topoIIα with an IC50 of 2 μM and for topoIIβ with an IC50 of 120 μM. It demonstrates activity against human cancer cell lines including melanoma (A375: 12.6 μM, G-361: 8.1 μM), breast (MCF7: 15.8 μM), endometrial (HeLa: 38.2 μM), lung (A549: 17.1 μM), and prostate (DU145: 11.5 μM) cancer cells. Following a single intraperitoneal injection of 10 mg kg, ARN-21934 achieves a peak plasma concentration of 0.68 μg mL in 15 minutes, with a half-life of 149 minutes, and remains detectable in plasma and the brain for up to 360 minutes. [1] Jose Antonio Ortega, et al. Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β. J Med Chem. 2020 Nov 12;63(21):12873-12886.

Topoisomerase II inhibitor 3 (Compound 6 h) is an acridone derivative acting as a Type II DNA topoisomerase (topo II) inhibitor. It specifically targets topo IIα β subtypes, with IC50 values of 0.17 μM for topo IIα and 0.23 μM for topo IIβ, causing significant DNA damage and inducing apoptosis by triggering the loss of mitochondrial membrane potential [1].

Topoisomerase II inhibitor 7, a potent inhibitor of the topoisomerase II alpha subtype, exhibits an IC50 of 3.19 μM. It effectively induces cell cycle arrest and apoptosis.

6,6′-Dihydroxythiobinupharidine, a cysteine proteases inhibitor, amplifies DNA cleavage facilitated by human topoisomerase IIα and IIβ by approximately 8-fold and 3-fold, respectively [1] [2].

5,7,3',5'-tetrahydroxy-6,4'-dimethoxyflavone exhibits anti-HIV-1 activity in the anti-syncytium assay using (∆Tat rev)MC99 virus and 1A2 cell line system, it shows considerably activity against HIV-1 reverse transcriptase. It exhibits cytotoxic activity against P-388 cell lines, it can inhibit DNA topoisomerase IIα activity, which may be responsible for the observed cytotoxicity.

Cannabidiol hydroxyquinone (HU-331) is potentially an active metabolite of cannabidiol that could play a role in inducing apoptosis. It functions by inhibiting the ATPase activity of topoisomerase IIα through a noncompetitive mechanism.