Biological Activity
Nutlin 3a is an active enantiomer of Nutlin-3, acts as a murine double minute (MDM2) antagonist that inhibits MDM2-p53 interactions and stabilizes the p53 protein, and thereby induces cell cycle arrest and apoptosis.
In Vitro
Nutlin 3a (Nutlin-3a) is a therapeutic which inhibits MDM2, activates wild-type p53, and induces apoptosis-as a therapeutic compound for TP53 wild-type ovarian carcinomas. Three cell lines (HOC-7, OVCA429 and A2780) with wild-type TP53 are highly sensitive to Nutlin 3a (IC50=4 to 6 μM). SKOV3 cells have an IC50 of 38 μM to Nutlin 3a. The two remaining ovarian clear cell lines (TOV21G and OVAS), both with TP53 wild-type, are relatively more sensitive to growth inhibition with Nutlin 3a (IC50=14 and 25 μm respectively) than the TP53 mutant cell lines[1]. Nutlin 3a (Nutlin-3a) is the active enantiomer of Nutlin-3. Nutlin 3a is a highly selective MDM2 antagonist and p53 inducer. Seven days of incubation with 10 μM Nutlin 3a leads to >90% inhibition of NIH/3T3 cells’growth but does not affect the proliferation of MEF in which both targets of the drug are eliminated. Nutlin 3a effectively arrestes cell-cycle progression in all cell lines, depleting the S-phase compartment to 0.2-2% and increasing the G1- and G2/M-phase compartments, indicating G1 and G2 arrest. The p53 targets p21 and MDM2 are elevated significantly 3 h after Nutlin 3a addition and reach maximal levels at 8 h. Nutlin 3a induces apoptosis in ≈60% of SJSA-1 and MHM cells after 40 h, which increase further after 60 h (85% and 65%, respectively)[2].
In Vivo
Nutlin 3a (Nutlin-3a) is efficacious in all models with average tumor growth inhibition ≥98%. Nutlin 3a suppresses xenograft growth in a dose-dependent fashion with the highest dose (200 mg/kg) showing a substantial tumor shrinkage (eight partial and one full regressions). The established SJSA-1 and MHM osteosarcoma xenografts with Nutlin 3a causes extensive tumor regression[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
