A new family of small molecules to probe the reactivation of mutant p53.
Cells that express mutant p53 derived from cancers are selectively killed by a new class of small organic molecules. The protein p53 is recognized as one of the most important guardians in the body that prevents tumor development. Mutant forms of p53 are present in approximately 50% of all human cancers. Molecules that selectively kill cells expressing mutant p53 could become important chemotherapeutic agents. Our research focuses on developing a synthetically accessible class of molecules that can be easily modified to examine structural activity relationships and mechanism of biological activity or to optimize for anticancer activity. In this communication, a new class of molecules that selectively arrests growth of cells expressing two forms of mutant p53 is described. Synthetic routes to these compounds are also presented.
Myers
Michael C
MC
Laboratory of Bioorganic Chemistry, NIDDK, NIH, DHHS, Bethesda, Maryland 20892, USA.
Wang
Jinling
J
Iera
Jaclyn A
JA
Bang
Jeong-Kyu
JK
Hara
Toshiaki
T
Saito
Shin'ichi
S
Zambetti
Gerard P
GP
Appella
Daniel H
DH
D000098:Acetophenones / Q000737:chemistry; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009154:Mutation; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000098:Acetophenones; D000588:Amines; D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007659:Ketones; D016159:Tumor Suppressor Protein p53; C055495:2-aminoacetophenone; C451219:2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one