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'''Nutlins''' are ''cis''-[[2-Imidazoline|imidazoline]] analogs which inhibit the interaction between [[mdm2]] and tumor suppressor [[p53]], and which were discovered by screening a chemical library by Vassilev ''et al.'' Nutlin-1, nutlin-2, and nutlin-3 were all identified in the same screen;<ref name="Nutlin">{{cite journal | vauthors = Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA | title = In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 | journal = Science | volume = 303 | issue = 5659 | pages = 844–8 | date = February 2004 | pmid = 14704432 | doi = 10.1126/science.1092472 | bibcode = 2004Sci...303..844V | s2cid = 16132757 }}</ref> however, Nutlin-3 is the compound most commonly used in anti-cancer studies.<ref name="annrev">{{cite journal | vauthors = Shangary S, Wang S | title = Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy | journal = Annual Review of Pharmacology and Toxicology | volume = 49 | pages = 223–41 | year = 2008 | pmid = 18834305 | pmc = 2676449 | doi = 10.1146/annurev.pharmtox.48.113006.094723 }}</ref> Nutlin small molecules occupy p53 binding pocket of MDM2 and effectively disrupt the p53–MDM2 interaction that leads to activation of the p53 pathway in p53 wild-type cells.<ref>{{cite journal | vauthors = Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, Myklebost O, Heimbrook DC, Vassilev LT | title = Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 6 | pages = 1888–93 | date = February 2006 | pmid = 16443686 | pmc = 1413632 | doi = 10.1073/pnas.0507493103 | doi-access = free }}</ref> Inhibiting the interaction between mdm2 and p53 stabilizes p53, and is thought to selectively induce a growth-inhibiting state called [[senescence]] in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or "wild-type" p53.{{Citation needed|date=April 2011}} Nutlin-3 has been shown to affect the production of p53 within minutes.<ref name="Leeuwen et al.">{{cite journal | vauthors = van Leeuwen IM, Higgins M, Campbell J, Brown CJ, McCarthy AR, Pirrie L, Westwood NJ, Laín S | title = Mechanism-specific signatures for small-molecule p53 activators | journal = Cell Cycle | volume = 10 | issue = 10 | pages = 1590–8 | date = May 2011 | pmid = 21490429 | doi = 10.4161/cc.10.10.15519 | publisher = Landes Bioscience | doi-access = free }}</ref>
The more potent of the two [[enantiomer]]s, nutlin-3a (
== References ==
{{Reflist}}
▲{{Use dmy dates|date=April 2011}}
[[Category:Imidazolines]]
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