ReACp53 is an inhibitor of p53 amyloid formation.
Nearly half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state.
In vitro: Previous study found that ReACp53 could penetrates into HGSOC primary cancer cells and convert mutant p53 from a punctate state into soluble wild-type-like p53. ReACp53 could also induce cell-dycle arrest, cancer cell death, resulting in p53 Degradation. Moreover, ReACp53 induced quich cell death in human primary uterine fibroblasts transfected with a R175H p53 mutant. In addition, ReACp53 was found to be able to specifically reduce the cell viability and proliferation of cancer cells with mutant but not wild-type p53 [1].
In vivo: Animal study showed that i.p. administered ReACp53 could rapidly enter the systemic circulation and could be detected in the mouse serum at the 1-hr time point. In addition, ReACp53 could be detected in tumor tissue. In efficacy models, tumor volumes monitored daily suggested that only ReACp53-treated OVCAR3 xenografts shrank whereas vehicle-treated tumors grew more than doubled in size. Moreover, mutant p53-bearing tumors in the ReACp53-treated mice were 80%–90% smaller in weight than the control cohort, further confirming the ability of ReACp53 to inhibit tumor proliferation in vivo [1].
Clinical trial: Up to now, ReACp53 is still in the preclinical development stage.
Reference:
[1] Soragni A et al. A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas. Cancer Cell. 2016 Jan 11;29(1):90-103.