GW4716

GW4716 is an acyl hydrazone small molecule that acts as a potent agonist of the estrogen-related receptors alpha (ERRα) and gamma (ERRγ). Beyond its role in metabolic and endocrine research, GW4716 has been investigated for its selective antineoplastic activity in p53-mutant cancer models. Research presented at AACR 2013 demonstrated that the compound selectively targets cancer cells harboring inactivating mutations in the TP53 gene, inducing G2/M phase arrest, mitotic catastrophe, and apoptosis. This cytotoxic effect is associated with the induction of MAPK signaling proteins, specifically p38 and MK2. In contrast, p53 wild-type cells exhibit a protective autophagic response when treated with GW4716, characterized by the induction of p53, p21, and the autophagy marker DRAM (Damage-Regulated Autophagy Modulator).