[6] Vernooij L, Bate-Eya LT, Alles LK, et al. High-Throughput Screening Identifies Idasanutlin as a Resensitizing Drug for Venetoclax-Resistant Neuroblastoma Cells[J]. Mol Cancer Ther, 2021, 20(6): 1161-1172. DOI:10.1158/...
While a number of p53-MDM2 inhibitors have progressed into clinical trials for the treatment of cancer, their progression has been hampered by a variety of problems, including acquired drug resistance, dose-dependent toxicity, and limited clinical efficiency. To make more progress, we integrated ...
performed dimethyl substitution of the imidalzoline core and replaced the methoxy group with a tert-butyl group to create the first investigational MDM2 inhibitor, RG7112.23 Preclinical evaluation of RG7112 demonstrated that the new drug activates the p53 pathway with a potent antitumor effect in ...
Cisplatin or BH3‑mimetics in combination with RG7388 were able to partially overcome acquired resistance to MDM2 inhibition in neuroblastoma cells A promising therapeutic strategy is the use of drug com- binations to prevent and overcome acquired resistance to monotherapy. The drugs ...
However no apoptosis is induced and Idasanutlin -treated U-2 OS cells can be cultured for long time periods in the presence of the drug. This prolonged treatment of U-2 OS cells leads to de novo generation of cell populations that escape from the cytostatic effect evoked by Idasanutlin ....
Bone marrow levels are 鈮 70% of plasma drug levels at steady state.CRs were seen in diverse pts, including varied risk groups, prior AHD, therapy-related AML (t-AML), p53 mt, R/R and de novo AML. All pts who achieved a CR during DE were relapse free for > 60 d. One pt on...
affording structurally diverse pyrrolidines bearing four contiguous stereocenters with stereo-diversity in generally high yields and good to excellent stereoselectivities(up to 98%yield,99:1 dr,>99%ee).Meanwhile,this strategy allowed the formal synthesis of antitumor drug RG7388(PhaseⅢclinical study)...
However, CCRF-CEM and p53 non-functional leukemic cells indicated drug resistance. Western blot analyses validated the bioinformatics results, confirming the downregulation of WIP1, p53 stabilization, as well as overexpression of p21WAF1 and Mdm2 proteins in Nalm6 cells transfected with miR-16-5p. ...
BH3-mimeticsRG7388The development of drug resistance reduces the efficacy of cancer therapy. Tumor cells can acquire resistance to MDM2 inhibitors, which are currently under clinical evaluation. We generated RG7388-resistant neuroblastoma cells, which became more proliferative and metabolically active and...
We speculate that our findings could lead to the development of newer treatments for breast and prostate cancers with drug combinations including HDACi.View Full-TextNatarajanRumbaugh-GoodwinUmamaheswariRumbaugh-GoodwinVenkatesanRumbaugh-GoodwinThiagarajan...