Nutlin

Nutlin 3

Names
IUPAC name (±)-4-[4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one
Other names Nutlin
Identifiers
CAS Number	548472-68-0 Y
3D model ( JSmol )	Interactive image
ChEMBL	ChEMBL191334 N
PubChem CID	16755649
UNII	53IA0V845C Y
SMILES CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl
Properties
Chemical formula	C30H30Cl2N4O4
Molar mass	581.49 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

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] 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.^[3] 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]} Nutlin-3 has been shown to affect the production of p53 within minutes.^[4]

The more potent of the two enantiomers, nutlin-3a ((–)-nutlin-3), can be synthesized in a highly enantioselective fashion.^[5] Several derivatives of nutlin, such as RG7112 and RG7388 (Idasanutlin) have been developed and progressed into human studies.^[6] Imidazoline core based on the methoxyphenyl substituents also stabilizes p53.^[7][8][9]

References