RITA | p53 Activator

RITA (reactivation of p53 and induction of tumor cell apoptosis, 213261-59-7) binds to p53 (K_d = 1.5 nM), changing its conformation, preventing it from binding to HDM2 and preventing its proteasomal degradation.¹ It also weakly (computed K_d = 22 µM) binds HDM2 in the cleft that contacts the p53 transactivation domain.² Its restoration of mutant p53 function depends on eIF2α phosphorylation, and it induces apoptosis via p53-dependent and -independent (JNK/SAPK/p38; protein translation) pathways.^3-5 Induces senescence in head and neck cancer cells.⁶

References:

1. Issaeva et al. (2004), Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors; Nat. Med., 10 1321
2. Espinoza-Fonseca et al. (2005), Targeting MDM2 by the small molecule RITA: towards the development of new multi-target drugs against cancer; Theor. Biol. Med. Model, 2 38
3. Ristau et al. (2019), RITA requires eIF2α-dependent modulation of mRNA translation for its anti-cancer activity; Cell Death Dis., 10 845
4. Zhao et al. (2010), Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA; Cell Cycle, 9 1847
5. Weilbacher et al. (2014), RITA can induce cell death in p53-defective cells independently of p53 function via activation of JNK/SAPK and p38; Cell Death Dis., 5 e1318
6. Chuang et al. (2014), The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells.; PLoS One, 9(8) e104821