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DRUG:

RG7112

i
Other names: RO5045337, RG7112
Associations
Company:
Roche
Drug class:
MDM2 inhibitor
Associations
26d
p53 and the E3 Ubiquitin Ligase MDM2 in Glaucomatous Lamina Cribrosa Cells. (PubMed, Int J Mol Sci)
MTT-assay showed equivocal cellular viability in NLC/GLC cells with/without RG-7112 treatment. Our data suggests that proliferation and the ubiquitin-proteasomal pathway are dysregulated in GLC cells, with MDM2-led p53 protein degradation negatively impacting its protective role.
Journal
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MDM2 (E3 ubiquitin protein ligase) • CASP3 (Caspase 3) • COL1A1 (Collagen Type I Alpha 1 Chain)
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TP53 expression
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RG7112
5ms
Strong activation of p53 by actinomycin D and nutlin-3a overcomes the resistance of cancer cells to the pro-apoptotic activity of the FAS ligand. (PubMed, Apoptosis)
Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112, and actinomycin D + idasanutlin had a similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD + Nut3a + FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.
Journal
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FASLG (Fas ligand) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • CASP10 (Caspase 10)
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etoposide IV • idasanutlin (RG7388) • dactinomycin • Nutlin-3 • RG7112
5ms
The Strong Activation of p53 Tumor Suppressor Drives the Synthesis of the Enigmatic Isoform of DUSP13 Protein. (PubMed, Biomedicines)
We demonstrated for the first time that mRNA expressed from this promoter actually produces the protein, which can be detected with Western blotting, in all examined cancer cell lines with wild-type p53 exposed to A + N. In some cell lines, it is also induced by clinically relevant camptothecin, by nutlin-3a acting alone, or by a combination of actinomycin D and other antagonists of p53-MDM2 interaction-idasanutlin or RG7112. This isoform, fused with green fluorescent protein, localizes in the perinuclear region of cells.
Journal
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TP53 (Tumor protein P53) • DUSP1 (Dual Specificity Phosphatase 1)
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idasanutlin (RG7388) • dactinomycin • Nutlin-3 • RG7112
over1year
Antagonizing MDM2 Overexpression Induced by MDM4 Inhibitor CEP-1347 Effectively Reactivates Wild-Type p53 in Malignant Brain Tumor Cells. (PubMed, Cancers (Basel))
Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest the combination of CEP-1347-induced MDM2 overexpression with the selective inhibition of MDM2's interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells.
Journal • Tumor cell
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MDM2 (E3 ubiquitin protein ligase) • MDM4 (The mouse double minute 4)
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TP53 wild-type • TP53 expression • MDM2 overexpression
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RG7112
over1year
Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs. (PubMed, Biomolecules)
Combining o-Vanillin and RG-7112 greatly enhanced the effect of either senolytic alone. Together, these results support the potential of senolytics as a promising treatment for IVD-related low back pain.
Journal
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CASP3 (Caspase 3)
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RG7112
2years
Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma. (PubMed, Front Oncol)
Multiple agents have been developed, including Nutlins such as RG7112 and small molecular inhibitors including SAR405838 and HDM201. Mechanisms of resistance are being elucidated, and novel inhibitors and combination therapies are currently under investigation. This review provides an overview of these strategies for targeting MDM2 in DDLPS.
Review • Journal • Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • MDM2 (E3 ubiquitin protein ligase)
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TMB-L • MDM2 amplification • MDM2 overexpression
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siremadlin (HDM201) • MI-773 • RG7112
over2years
Establishment and evaluation of retroperitoneal liposarcoma patient-derived xenograft models: an ideal model for preclinical study. (PubMed, Int J Med Sci)
Treatment with MDM2 inhibitor RG7112 significantly suppressed tumor growth of DDLPS PDX in mice. In conclusion, we successfully established RLPS PDX models that were histologically, genetically, and molecularly consistent with the original tissues. These models might provide opportunities for advancing RLPS tumor biology research, facilitating the development of novel drugs, particularly those targeting MDM2 amplification, adipose differentiation process, angiogenesis, cancer-associated fibroblasts, and so on.
Preclinical • Journal
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MDM2 (E3 ubiquitin protein ligase)
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MDM2 amplification
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RG7112
over2years
p53 mA modulation sensitizes hepatocellular carcinoma to apatinib through apoptosis. (PubMed, Apoptosis)
Here, we found that p53 n6-methyladenosine (mA) played a decisive role in regulating HCC sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. Importantly, we observed that downregulation of METTL3 and upregulation of p53 expression by oral administration of chemotherapy drugs triggered apoptosis and xenograft tumor growth inhibition in nude mice. Based on these findings, we hypothesize that a METTL3-mA-p53 axis could be a potential target in HCC therapy.
Journal
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METTL3 (Methyltransferase Like 3)
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TP53 expression
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AiTan (rivoceranib) • RG7112
over3years
An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression. (PubMed, Cell Death Dis)
We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • CHEK2 (Checkpoint kinase 2)
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TP53 mutation • TP53 expression
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Nutlin-3 • RG7112
almost4years
FGFR/RACK1 interacts with MDM2, promotes P53 degradation, and inhibits cell senescence in lung squamous cell carcinoma. (PubMed, Cancer Biol Med)
Together, our findings revealed the regulatory roles and mechanisms of FGFR/RACK1 in cell senescence. This understanding should be important in the treatment of LSCC.
Journal
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FGFR (Fibroblast Growth Factor Receptor) • MDM2 (E3 ubiquitin protein ligase) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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TP53 expression
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RG7112