Murine double minute

Lu et u/. screened a prefiltered set of 11000 compounds from the NCI database with a pharmacophore model based on the crystal structure of murine double minute 2 (MDM2) oncoprotein in complex with the p53 tumor suppressor and several non-peptide small inhibitors. The remaining compounds were docked, scored, and 67 compounds were selected for testing, ten of which were active in a competitive binding assay. Similarly, Yu et used a Catalyst HipHop model combined with the molecular shape of an experimental X-ray... 

Hardcastle IR, Liu J, Valeur E et al (2011) Isoindolinone inhibitors of the murine double minute 2 (MDM2)-p53 protein-protein interaction structure-activity studies leading to improved potency. J Med Chem 54 1233-1243... 

Binder BR (2007) A novel application for murine double minute 2 antagonists the p53 tumor suppressor network also controls angiogenesis. Circ Res 100 13-14... 

Drakos E, Thomaides A, Medeiros LJ et al (2007) Inhibition of p53-murine double minute 2 interaction by Nutlin-3A stabilizes p53 and induces cell cycle arrest and apoptosis in Hodgkin lymphoma. Clin Cancer Res 13 3380-3387... 

MDM2 (murine double minute 2) Enhances radiosensitivity A549 cell Une 144... 

Sarcoglycan gene sarcolemmal ay-sarcoglycan protein deficiencies (loss-or-function point mutations familial, vertical somatic, acquired). For mice with dystrophin and sarcoglycan deficiencies Sgca developing embryonal rhabdomyosarcoma with excess of murine double minute MDM-2 protein and missense-mutated p53, chck Fernandez K et al Am J Pathol 2010 176 416-434. 

MDM, murine double minute protein with human homolog, neutralizes p53 protein marking it for ubiquitylation (Figure 64). Click for MDM/p53 protein complex rheostat by Eischen CM Lozano G. In FAK (focal adhesion kinase) protein complex, p53 protein is inactive. Click for R2 (Roslin) dismpting FAK/p53 protein complex and liberating p53 protein for action (to block tumor growth) by Golubovskaya VM Ho B Conroy J et al. 

A series of sulfamide benzodiazepines 204 have been prepared and their p5 3-murine double minute 2 (MDM2) inhibitory activity and in vitro antitumor activity were evaluated (14MI15741). These heterocycles demonstrated moderate inhibition of p53 MDM2 protein—protein interaction. Intramolecular 1,3-dipolar cycloaddition of a l-(azidoarylsulfonyl)-2-alke-nyl pyrrolidine yielded aziridino-fused pyrrolo[l,2,5]benzothiadiazepine 205 as the only isolable product this system and other henzodiazepines are under investigation for antitumor and antibiotic potential (14MOL16737). 

---