Desethylamiodarone

Desethylamiodarone (N-Desethylamiodarone; LB 33020) is the major active metabolite of Amiodarone (HY-14187) generated via CYP3A4 metabolism. Desethylamiodarone downregulates p‑Akt, p‑Bad and Bcl‑2, upregulates Bax, promotes mitochondrial release of cytochrome c, activates caspase‑3 and cleaves PARP‑1, thereby inducing cell cycle arrest and apoptosis. Desethylamiodarone can be used in cervical cancer-related research^[1][2][3]. In Vitro:Desethylamiodarone (DEA) (2.5-10 μM; 24-72 h) reduces the viability of human cervical cancer HeLa cells in a dose- and time-dependent manner^[1].
Desethylamiodarone (0.5-2 μM; 7 days) inhibits colony formation of human cervical cancer HeLa cells in a dose-dependent manner^[1].
Desethylamiodarone (2.5-5 μM; 24 h) inhibits the PI3K-Akt pathway in human cervical cancer HeLa cells in a dose-dependent manner by reducing the phosphorylation levels of Akt and its downstream target Bad; it also regulates the expression of apoptosis-related proteins in human cervical cancer HeLa cells in a dose-dependent manner: downregulating Bcl-2, upregulating Bax, inducing cytochrome c release, and activating the cleavage of caspase-3 and PARP-1^[1].
Desethylamiodarone (5-10 μM; 24 h) induces apoptosis-related nuclear morphological changes (pyknosis and fragmentation) in human cervical cancer HeLa cells; it also induces apoptosis in human cervical cancer HeLa cells in a dose-dependent manner^[1].
Desethylamiodarone (5 μM; 24 h) induces G0/G1 cell cycle arrest in human cervical cancer HeLa cells^[1].
Desethylamiodarone (2.5-12.5 μg/mL; 1-4 days) exerts strong direct cytotoxicity against human thyroid cell line SGHTL-34 cultured in vitro, with an EC₅₀ of 6.8 μg/mL at 24 h. It reduces cell numbers through cell destruction rather than decreasing cell adhesion, and induces vacuolization after 4 days of exposure^[2].
Desethylamiodarone exhibits strong direct cytotoxicity against primary human retro-orbital fibroblasts in vitro, and a reduction in cell number is detected via protein content assay after 4 days of exposure^[2]. In Vivo:Desethylamiodarone (100 mg/kg; i.p.; 30 min prior to testing) has brain concentrations significantly increased by Oxcarbazepine (HY-B0114) and Pregabalin in mice^[3].