KG-548 is an ARNT/TACC3 disruptor as well as a HIF-1α inhibitor. KG-548 directly interferes with the formation of the ARNT/TACC3 complex by competitively binding the ARNT PAS-B domain with TACC3. ARNT is the aryl hydrocarbon receptor nuclear translocator which is also known as HIF-β [1][2].

HIF is a heterodimer of two bHLH-PAS (basic Helix Loop Helix-Per-ARNT-Sim) subunits, including a HIF-α paralog (HIF-1α, -2α, -3α) and aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF-β) [1]. KG-548 (0-250 μM; 16 h for over night) exhibits the great reduction of ARNT/CCC complex formation for both coactivators, and also disrupts ARNT2 PAS-B/TACC3 interactions [1]. KG-548 (0-2 mM; 16 h for over night) dose-dependently breaks up the (320 μM) ARNT PAS-B/TACC3 complex in vitro and in cell lysate with an IC 50 value of 25 μM [1]. KG-548 significantly inhibits lactate production of glycolysis on in FaDu hypopharyngeal carcinoma cells [2]. Western Blot Analysis [1] Cell Line: HEK293T cell lysates Concentration: 0, 5, 50, 100, 250, 500 μM and 1 mM, 2 mM Incubation Time: 16 hours Result: Weakened the ARNT/TACC3 interaction from 5 μM to 500 μM dose-dependently, and decreased the protein intense of ARNT associated with immunoprecipitated TACC3 protein by 82% (500 μM), 59% (1 mM), 43% (2 mM), respectively.