P53-MDM2 antagonist

Fungi - Fusarium sp. Chiorofusin - peptide-based 284-286 p53-MDM2 antagonist... 

Duncan SJ, Griischow S, Williams DH, McNicholas C, Purewal R, Hajek M, Gerlitz M, Martin S, Wrigley SK, Moore M (2001) Isolation and Stmcture Elucidation of a Chloro-fusin, a Novel p53-MDM2 Antagonist from a Fusarium sp. J Am Chem Soc 123 554... 

Williams, C. McNicholas, R. Purewal, M. Hajek, M. Gerlitz, S. Martin, S.K. Wrigley, M. Moore, Isolation and structure elucidation of chlorofusin, a novel p53-mdm2 antagonist from a Fusarium sp, J. Am. Chem. Soc. 2001, 123, 554-560. 

Vassilev LT. Small-molecule antagonists of p53-MDM2 binding ... 

Popowicz GM, Czama A, Wolf S et al (2010) Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery. Cell Cycle 9 1104-1 111... 

Tovar C, Rosinski J, Filipovic Z et al (2006) Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer implications for therapy. Proc Natl Acad Sci USA 103 1888-1893... 

Carvajal D, Tovar C, Yang H et al (2005) Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors. Cancer Res 65 1918-1924... 

Coll-Mulet L, Iglesias-Serret D, Santidrian AF et al (2006) MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood 107 4109-4114... 

Kojima K, Konopleva M, Samudio IJ et al (2005) MDM2 antagonists induce p53-dependent apoptosis in AML implications for leukemia therapy. Blood 106 3150-3159... 

Gu L, Zhu N, Findley HW, Zhou M. MDM2 antagonist nutin-3 is a potent inducer of apoptosis in pediatric acute lymphoblastic leukemia cells with wild-type p53 and overexpression of MDM2. Leukemia. 2008 22 730-9. 

Renouf B, Hollville E, Pujals A, Tetaud C, Garibal J, Wiels J. Activation of p53 by MDM2 antagonist has di f(raential apoptotic effects on Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt s lymphoma cells. Leukemia. 2009 23 1557-63. 

Vassilev, L. T. (2004). Small-molecule antagonists of p53-MDM2 binding research tools and potential therapeutics. Cell Cycle 3 419-421 Apr. 

MDM2 Protein antagonist of p53 tumor suppressor protein Sarcomas... 

Vassilev FT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Fukacs C, Klein C, Fotouhi N, Fiu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004 303 844-848. 

Subsequent to having the desired a,a-diallq lated amino acids available, the synthesis of hydrocarbon-stapled peptides is relatively straightforward and employs solid-phase peptide chemistiy, as illustrated for ATSP-7041 (Scheme 9.2), to provide a feasible route for chemical development. As further detailed below, the hydrocarbon-stapled peptide ATSP-7041 is a dual MDM2/MDMX antagonist that exhibits high potency in vitro and efficacy in vivo in p53-dependent cancer models. 

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