Background:

K-80003 is a potent inhibitor of tRXRα-dependent Akt activation and cancer cell growth.

When MCF-7 cells are cotreated with K-80003, TNFα-induced colocalization of tRXRα with p85α in the cytoplasm is inhibited, resulting in tRXRα nuclear localization. Western blotting shows that K-80003-stabilized tetrameric form of tRXRα is found exclusively in the nuclear fraction, while tRXRα monomer is distributed both in the nuclear and cytoplasmic fractions[2].

K-80003 is a potent inhibitor of AKT activation by all-trans-retinoic acid. K-80003 displays enhanced efficacy in inhibiting tRXRα-dependent AKT activation and tRXRα tumor growth in animals. K-80003 has high affinity to RXRα but lacks COX inhibitory activity[1].

[1]. Zhou H, et al. NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. Cancer Cell. 2010 Jun 15;17(6):560-73. [2]. Chen L, et al. Modulation of nongenomic activation of PI3K signalling by tetramerization of N-terminally-cleaved RXRα. Nat Commun. 2017 Jul 17;8:16066.