Nutlin
Encyclopedia
Nutlins are cis-imidazoline
analogs which inhibit the interaction between mdm2
and tumour suppressor p53
, and 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, however Nutlin-3 is the compound most commonly used in anti-cancer studies.. 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. Nutlin-3 has been shown to affect the production of p53 within minutes.
Imidazoline
Imidazoline is a nitrogen-containing heterocycle with formula C3H6N2, derived from imidazole. The ring contains an imine bond, and the carbons at the 4 and 5 positions are singly bonded, rather than doubly bonded for the case of imidazole...
analogs which inhibit the interaction between mdm2
Mdm2
Mdm2 is an important negative regulator of the p53 tumor suppressor. It is the name of a gene as well as the protein encoded by that gene. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain of the p53 tumor suppressor and an inhibitor of...
and tumour suppressor p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, and 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, however Nutlin-3 is the compound most commonly used in anti-cancer studies.. Inhibiting the interaction between mdm2 and p53 stabilizes p53 and is thought to selectively induce a growth-inhibiting state called senescence
Senescence
Senescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...
in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or wild type p53. Nutlin-3 has been shown to affect the production of p53 within minutes.