Nutlin-3a, the active enantiomer of Nutlin-3, is a robust inhibitor of murine double minute (MDM2) with an IC50 of 90 nM. It blocks the interactions between MDM2 and p53, thereby stabilizing the p53 protein, and leads to the induction of cell autophagy and apoptosis. Nutlin-3a is considered promising for research into TP53 wild-type ovarian carcinomas[1][2]. Nutlin-3a serves as a therapeutic agent that inhibits MDM2, activates wild-type p53, and triggers apoptosis, making it a potential treatment for TP53 wild-type ovarian carcinomas. Three cell lines with wild-type TP53—HOC-7, OVCA429, and A2780—show high sensitivity to Nutlin-3a, with IC50 values ranging from 4 to 6 μM. SKOV3 cells present an IC50 of 38 μM in response to Nutlin-3a. Additionally, the two other ovarian clear cell lines with TP53 wild-type, TOV21G and OVAS, exhibit relatively higher sensitivity to Nutlin-3a-induced growth inhibition, with IC50 values of 14 μM and 25 μM, respectively, compared to TP53 mutant cell lines[1]. After seven days of incubation with 10 μM Nutlin-3a, there is more than 90% inhibition of NIH/3T3 cells' growth, while the proliferation of MEF cells, which lack both targets of the drug, remains unaffected. Nutlin-3a effectively halts cell-cycle progression across all cell lines, reducing the S-phase compartment to 0.2-2% and enlarging the G1- and G2/M-phase compartments, indicative of G1 and G2 arrest. The p53 targets, p21 and MDM2, show a significant increase just 3 hours after the addition of Nutlin-3a and reach peak levels at 8 hours. Nutlin-3a triggers apoptosis in approximately 60% of SJSA-1 and MHM cells after 40 hours, with the percentage rising after 60 hours to 85% and 65%, respectively[2].
Nutlin-3a 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
22RV1
Growth Inhibition Assay
IC50=12.8059 μM
SANGER
697
Growth Inhibition Assay
IC50=5.4455 μM
SANGER
A101D
Growth Inhibition Assay
IC50=2.3501 μM
SANGER
A172
Growth Inhibition Assay
IC50=2.67588 μM
SANGER
Nutlin-3a 动物研究
Animal study
Nutlin-3a proves to be effective across all models, achieving an average tumor growth inhibition of ≥98%. It diminishes xenograft growth in a dose-responsive manner, with the highest administered dose of 200 mg/kg resulting in significant tumor reduction, including eight partial and one complete regressions. Treatment with Nutlin-3a in established SJSA-1 and MHM osteosarcoma xenografts leads to extensive tumor regression[2].
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