In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

By L. Vassilev, B. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, Norman Kong, U. Kammlott, C. Lukacs, C. Klein and 2 more. Science, 2004

4,592 citations recorded by the source corpus.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/c680f78cd2ab766c7df8b965b88b04a040ed70fc

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Citations in the corpus

Ubiquitin: structures, functions, mechanisms. (2004, background): “The E3/substrate interface, which is likely to be idiosyncratic, is also an attractive drug target [137].”
TIGAR, a p53-inducible regulator of glycolysis and apoptosis. (2006, background): “To further assess the ability of TIGAR to modulate p53-induced apoptosis, we examined the effect of treatment of the cells with Nutlin-3, a direct and specific activator of p53 (Vassilev et al., 2004).”
MDM2 and CDK4 Immunostainings Are Useful Adjuncts in Diagnosing Well-Differentiated and Dedifferentiated Liposarcoma Subtypes: A Comparative Analysis of 559 Soft Tissue Neoplasms With Genetic Data (2005, methodology): “An alternative way to treat these patients with DDLPS could be the use of selective inhibitors of MDM2 and CDK4 proteins.(24,39) It has been demonstrated that these molecules play a significant role in cell cycle regulatory mechanisms, especially in restoring the functions of crucial genes such as p”
Cyclin D as a therapeutic target in cancer (2011, methodology): “It may also be possible to identify low-molecular-mass inhibitors of cyclin–CDK substrate interactions using high-throughput screens that are similar to those used for the discovery and preclinical testing of inhibitors of MDM2–p53 binding (nutlins”
Cellular Senescence: Aging, Cancer, and Injury. (2019, background): “(325)] has inspired other researchers to design new MDM2 inhibitors with higher selectivity and potency and an improved pharmacokinetics.”
p53 ubiquitination: Mdm2 and beyond. (2006, background): “More importantly, modulations of the p53 and Mdm2 interaction have been proven essential for p53 activation, as shown by the small molecule inhibitor Nutlin (Vassilev et al., 2004).”
Promoting apoptosis as a strategy for cancer drug discovery (2005, background): “However, a more potent (50% inhibitory concentration (IC 50 ) = 100 nM) small-molecule MDM2 inhibitor was recently discovered within a series of cis -imidazoline analogues called the Nutlin”
Structure-based maximal affinity model predicts small-molecule druggability (2007, background): “01 0.1 1 10 Neuraminidase (5) PTP-1b (5) Cathepsin K (2) HMG CoA (6) DNA gyrase (2) Aldose reductase (3) HIV Protease (4) AChE (2) fCyp 51(2) CDK-2 (6) PDE-4D (4) Enoyl reductase (2) PDE-5 (2) NNRTI (4) MAP POD (nM) a b c 10 4 10 4 10 3 10 2 10 2 0.01 1 10 2 10 4”
Reaching for high-hanging fruit in drug discovery at protein–protein interfaces (2007, background): “2 ; Table 1 ), was found to disrupt HDM2–p53 complexes with an IC 50 of 90 nM, and it showed potent p53-blocking activity in vitro and activity against tumour xenografts in vivo”