Serefs’ preprint paper is published on BioRxiv. This paper is entitled “Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice” and describes discovery of a molecule, M47, selectively reduces half- life of mammalian Cryptochrome 1.
M47 enhanced the effect of oxaliplatin in p53 null mouse skin fibroblast (MSF) cells.
(A) Ras pT24 transformed p53 null MEF fibroblast cells were treated with 0, 10 or 20µM oxaliplatin and incubated for 24h. Then either DMSO or M47 was added and incubated for 16h. Cells were lysed and analyzed via protein immunoblot technique. At each cases M47 increases the cleaved PARP protein level and decreases CRY1 levels. Bar graph was drawn normalizing to 10µM dosage of oxaliplatin (Data represent the mean ± SEM, n=4 **: p < 0.005, versus DMSO control by two-way ANOVA). (B) M47 in p53−/−mice reduces age adjusted tumor incidence. Kaplan–Meier survival analysis (log-rank test) of the time of death with evidence of tumors showed significant differences between vehicle treated p53−/− and M47 treated p53−/− (**p<0,01)