atiprimod

Atiprimod is an orally bioavailable small molecule of the azaspirane class with anti-inflammatory, antineoplastic, and antiangiogenic properties. It was initially developed by Smith Kline and French Laboratories (later GlaxoSmithKline) for rheumatoid arthritis but development for this indication was discontinued in early clinical trials. Atiprimod has been investigated in phase I and II studies for multiple myeloma, neuroendocrine carcinoma, mantle cell lymphoma, and other advanced cancers. Mechanistically, it inhibits phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby blocking interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) signaling pathways. This leads to downregulation of anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1; inhibition of cell proliferation; induction of cell cycle arrest; apoptosis via both caspase-dependent mitochondrial pathways as well as caspase-independent AIF-mediated mechanisms; suppression of angiogenesis through VEGF inhibition; and downregulation of additional tumor-promoting cytokines such as TNF-alpha[1][4][5][6][7].

Other names

azaspirane123018-47-3atiprimod [INN]atiprimod (free base)