Milademetan (DS-3032) can stabilize TP53 and selectively induce CDKNA1, BAX and MDM2 expression in neuroblastoma cells with wild-type TP53[3].Milademetan (DS-3032b) treatment enhances TP53 target gene expression and induces G1 cell cycle arrest, senescence and apoptosis[3].Milademetan (DS-3032b, 0-2000 nM) treatment selectively inhibits viability, proliferation and migration of neuroblastoma cells with wildtype TP53 independently of MYCN status[4].

Milademetan (DS-3032b, 50 mg/kg, oral gavage) delays tumor growth and improves survival in mice xenografted with neuroblastoma cells with functional TP53[4].

[1]. ARYL SULFONOHYDRAZIDES. WO 2017069289 A1. [2]. M.M. Gounder, et al. Milademetan, an oral MDM2 inhibitor, in well-differentiated/dedifferentiated liposarcoma: results from a phase 1 study in patients with solid tumors or lymphomas. European Journal of Cancer 138S2 (2020) S1-S62. [3]. Li, Yangbing, et al. Development of novel PROTAC Small-Molecule Degraders of MDM2 Protein and Peptidomimetic Inhibitors Targeting WDR5-MLL1 Protein-Protein Interaction. [4]. Viktor Arnhold, et al. Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma. ncotarget. 2018 Jan 5; 9(2): 2304-2319.

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