ARN-21934

ARN-21934 is a potent, highly selective, blood-brain barrier (BBB) penetrant inhibitor for human topoisomerase II ? over ?. It inhibits DNA relaxation with an IC50 of 2 ?M, compared to 120 ?M for Etoposide. ARN-21934 exhibits favorable in vivo pharmacokinetic properties and shows promise in anticancer research, displaying affinity for topoII? with an IC50 of 2 ?M and for topoII? with an IC50 of 120 ?M. It demonstrates activity against human cancer cell lines including melanoma (A375: 12.6 ?M, G-361: 8.1 ?M), breast (MCF7: 15.8 ?M), endometrial (HeLa: 38.2 ?M), lung (A549: 17.1 ?M), and prostate (DU145: 11.5 ?M) cancer cells. Following a single intraperitoneal injection of 10 mg/kg, ARN-21934 achieves a peak plasma concentration of 0.68 ?g/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 ? over ?. J Med Chem. 2020 Nov 12;63 (21) :12873-12886.