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Nutlins are cis-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;[1] however, Nutlin-3 is the compound most commonly used in anti-cancer studies.[2] Inhibiting the interaction between mdm2 and p53 stabilizes p53, and is thought to selectively induce a growth-inhibiting state calledsenescence in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or "wild-type" p53.[citation needed] Nutlin-3 has been shown to affect the production of p53 within minutes.[3]
The more potent of the two enantiomers, (−)-nutlin-3, can be synthesized in a highly enantioselective fashion.[4]Several derivatives of nutlin, such as RG7112 and RG7388 have been developed and progressed into human studies.
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