milademetan-free-base

Description: Milademetan tosylate (DS-3032b; DS-3032) is a potent, selective and orally bioactive MDM2 inhibitor with potential antitumor activity. DS-3032b binds to, and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this MDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis.

References:

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. Oncotarget. 2018 Jan 5; 9(2): 2304–2319.

5. Predictive gene signatures determine tumor sensitivity to MDM2 inhibition. Cancer Res. 2018 Feb 28. pii: canres.0949.2017. doi: 10.1158/0008-5472.

Related CAS #: 1398568-47-2 (free base) 2095625-97-9 (tosylate hydrate) 1398569-75-9 (tosylate)