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DRUG:

idasanutlin (RG7388)

i
Other names: RG7388, RO5503781, RG-7388, RG 7388, RO-5503781, RO 5503781
Company:
Roche
Drug class:
MDM2 inhibitor
3d
Trial termination
|
TP53 (Tumor protein P53)
|
TP53 wild-type
|
Venclexta (venetoclax) • cytarabine • cyclophosphamide • topotecan • idasanutlin (RG7388) • fludarabine IV
3ms
Managing the unmanageable: evidence-driven approaches to real-world patient prototypes of TP53-mutant myelodysplastic neoplasms and acute myeloid leukemia. (PubMed, Leukemia)
The debate regarding whether allogeneic stem cell transplant should be offered to these patients is summarized. Finally, this review explores the recent unfortunate news of pauses in clinical trials for the leading investigational agents - eprenetapopt, magrolimab, sabatolimab, and idasanutlin - and offers solutions toward re-invigorating the pipeline of precision therapeutics in 2025.
Review • Journal • Real-world evidence • Real-world
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
eprenetapopt (APR-246) • idasanutlin (RG7388) • magrolimab (ONO-7913) • sabatolimab (MBG453)
3ms
Targeting MDM2-mediated suppression of p53 with idasanutlin: a promising therapeutic approach for acute lymphoblastic leukemia. (PubMed, Invest New Drugs)
In this research, RG7388 was investigated with pre-clinical methods in ALL cells as a novel treatment strategy. This study suggests further functional research and in-vivo evaluation, and it highlights the prospect of treating p53-functional ALL with MDM2 inhibitors.
Journal
|
CASP3 (Caspase 3) • CASP7 (Caspase 7)
|
TP53 mutation • TP53 wild-type • TP53 expression
|
idasanutlin (RG7388)
3ms
Trial completion • Combination therapy
|
GDF15 (Growth differentiation factor 15)
|
Ninlaro (ixazomib) • idasanutlin (RG7388)
4ms
BH3-mimetics or DNA-damaging agents in combination with RG7388 overcome p53 mutation-induced resistance to MDM2 inhibition. (PubMed, Apoptosis)
This mutation abated its transcriptional activity via destabilization of the tetrameric p53-DNA complex and was observed in many cancer types. Finally, we found that Cisplatin and various BH3-mimetics could enhance RG7388-mediated apoptosis in RG7388-resistant neuroblastoma cells, thereby partially overcoming resistance to MDM2 inhibition.
Journal • Combination therapy
|
TP53 (Tumor protein P53)
|
cisplatin • idasanutlin (RG7388)
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
|
FASLG (Fas ligand) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • CASP10 (Caspase 10)
|
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
|
TP53 (Tumor protein P53) • DUSP1 (Dual Specificity Phosphatase 1)
|
idasanutlin (RG7388) • dactinomycin • Nutlin-3 • RG7112
5ms
RNA Sequencing Reveals Candidate Genes and Pathways Associated with Resistance to MDM2 Antagonist Idasanutlin in TP53 Wild-Type Chronic Lymphocytic Leukemia. (PubMed, Biomedicines)
Furthermore, differential expression of certain genes was detected, which could serve as the backbone for novel combination treatment approaches. This research provides preclinical data to guide the exploration of drug combination strategies with MDM2 inhibitors, leading to future clinical trials and associated biomarkers that may improve outcomes for CLL patients.
Journal
|
TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
|
idasanutlin (RG7388)
6ms
Trial completion • Trial completion date • Combination therapy
|
TP53 (Tumor protein P53)
|
Venclexta (venetoclax) • cytarabine • cyclophosphamide • topotecan • idasanutlin (RG7388) • fludarabine IV
6ms
Optimizing Drug Combinations for T-PLL: Restoring DNA Damage and P53-Mediated Apoptotic Responses. (PubMed, Blood)
Current treatments, i.e. the CD52-antibody alemtuzumab, offer transient responses, with relapses being almost inevitable without consolidating allogeneic transplantation...Overall, the most efficient/selective single-agents and combinations (in vitro and in mice) in-cluded Cladribine, Romidepsin ((H)DAC), Venetoclax (BCL2), and/or Idasanutlin (MDM2)...Our data emphasize the therapeutic potential of pharmacologic strategies to reinstate P53-mediated apoptotic responses. The identified efficacies and their synergies provide an informative background on compound and patient selection for trial designs in T-PLL.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2)
|
Venclexta (venetoclax) • Campath (alemtuzumab) • cladribine • idasanutlin (RG7388) • Istodax (romidepsin)
6ms
Trial primary completion date • Combination therapy
|
TP53 (Tumor protein P53)
|
Venclexta (venetoclax) • cytarabine • cyclophosphamide • topotecan • idasanutlin (RG7388) • fludarabine IV
9ms
Combination p53 activation and BCL-xL/BCL-2 inhibition as a therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia. (PubMed, Leukemia)
Utilizing high-throughput combination screening of 1971 FDA-approved and clinically advanced compounds, we identified BCL-xL/BCL-2 inhibitor navitoclax as the most promising idasanutlin combination partner. We demonstrate a preferential engagement of cell death over G1 cell cycle arrest, mechanistically implicating MCL-1-binding pro-apoptotic sensitizer NOXA. The proposed combination of two clinical-stage compounds independently under clinical evaluation for ALL is of high clinical relevance and warrants consideration for the treatment of patients with high-risk and relapsed ALL.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
|
TP53 mutation • TP53 wild-type
|
navitoclax (ABT 263) • idasanutlin (RG7388)
9ms
Enrollment closed • Enrollment change • Combination therapy
|
TP53 (Tumor protein P53)
|
TP53 wild-type
|
Venclexta (venetoclax) • cytarabine • cyclophosphamide • topotecan • idasanutlin (RG7388) • fludarabine IV
9ms
Trial of Idasanutlin and Selinexor Therapy for Children With Progressive/Relapsed AT/RT or Extra-CNS Malignant Rhabdoid Tumors (clinicaltrials.gov)
P1, N=0, Withdrawn, St. Jude Children's Research Hospital | N=52 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal
|
Xpovio (selinexor) • idasanutlin (RG7388)
11ms
MDM2 Antagonist Idasanutlin Reduces HDAC1/2 Abundance and Corepressor Partners but Not HDAC3. (PubMed, ACS Med Chem Lett)
Although two MDM2-recruiting heterobifunctional molecules reduced HDAC1 and HDAC2 abundance with complete selectivity over HDAC3 and reduced HDAC1/2 corepressor components LSD1 and SIN3A, we were surprised to observe that idasanutlin alone was also capable of this effect. This finding suggests an association between the MDM2 E3 ligase and HDAC1/2 corepressor complexes, which could be important for designing future dual/bifunctional HDAC- and MDM2-targeting therapeutics, such as PROTACs.
Journal
|
HDAC2 (Histone deacetylase 2) • HDAC1 (Histone Deacetylase 1) • HDAC3 (Histone Deacetylase 3)
|
idasanutlin (RG7388)
12ms
Trial completion date • Trial initiation date • Trial primary completion date
|
Xpovio (selinexor) • idasanutlin (RG7388)
1year
High Throughput Microfluidics Platform to Assess Synthetic Lethality and Novel Therapeutic Drug Combinations (ASH 2023)
In the context of acute myeloid leukemia (AML) specifically, several efficacious combination therapies have been approved for specific patient subsets, such as all-trans retinoic acid (ATRA) plus arsenic trioxide in the PML-RARA fusion acute promyelocytic subtype and Midostaurin plus Cytarabine and Daunorubicin in FLT3-mutant AML. Strong established hits in our screen include ATR inhibition plus Gemcitabine treatment as well as several combinations involving the BCL-2 inhibitor Venetoclax with chemotherapies (Decitabine and Daunorubicin), Quizartinib, Idasanutlin, and mTOR inhibitors. Thus, we have developed an efficient and cost-effective high throughput drug combinations profiling system that has uncovered candidate therapies that may expand treatment options for patients afflicted by AML.
IO biomarker • Synthetic lethality
|
FLT3 (Fms-related tyrosine kinase 3) • PML (Promyelocytic Leukemia)
|
FLT3 mutation • PML-RARA fusion
|
Venclexta (venetoclax) • gemcitabine • cytarabine • Rydapt (midostaurin) • Vanflyta (quizartinib) • decitabine • daunorubicin • idasanutlin (RG7388) • arsenic trioxide
1year
Idasanutlin and navitoclax induce synergistic apoptotic cell death in T-cell acute lymphoblastic leukemia. (PubMed, Leukemia)
Combination treatment with idasanutlin and navitoclax, a potent Bcl-2/Bcl-xL inhibitor, induces more consistent and potent synergistic killing of T-ALL PDX lines in vitro than venetoclax, a Bcl-2 specific inhibitor. Moreover, a marked synergic response to combination treatment with idasanutlin and navitoclax was seen in vivo in all four T-ALL xenografts tested, with a significant increase in overall survival in the combination treatment group. Collectively, these preclinical data show that the combination of idasanutlin and navitoclax is highly active in T-ALL and may merit consideration in the clinical setting.
Journal • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein) • BBC3 (BCL2 Binding Component 3)
|
TP53 mutation • MYC expression • NOTCH mutation
|
Venclexta (venetoclax) • navitoclax (ABT 263) • idasanutlin (RG7388)
1year
Trial of Idasanutlin and Selinexor Therapy for Children With Progressive/Relapsed AT/RT or Extra-CNS Malignant Rhabdoid Tumors (clinicaltrials.gov)
P1, N=52, Not yet recruiting, St. Jude Children's Research Hospital | Phase classification: P1b --> P1
Phase classification
|
Xpovio (selinexor) • idasanutlin (RG7388)
1year
TRIP13 Is a Fetal-Enriched Therapeutic Target in NUP98-JARID1A+ Pediatric Non-Down Syndrome AMKL (ASH 2023)
To exploit our mechanistic knowledge on TRIP13 ablation-mediated P53 activation, we further combined DCZ0415 with the MDM2 inhibitor Idasanutlin. In line with our mechanistic data, a high synergy (Bliss synergy score = 9.7) of TRIP13 and MDM2 inhibition was observed. In conclusion, our study uncovers TRIP13 as a fetal-enriched vulnerability in NJ-driven non-DS-AMKL, mechanistically acting through P53, which we leveraged for a mechanism-driven treatment approach with dual TRIP13/MDM2 inhibition as a potential therapeutic strategy for the treatment of high-risk pediatric non-DS-AMKL.
Clinical
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • ARID1A (AT-rich interaction domain 1A) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • KDM5A (Lysine Demethylase 5A) • TRIP13 (Thyroid Hormone Receptor Interactor 13)
|
idasanutlin (RG7388)
1year
Durable Clinical Benefits of Idasanutlin Therapy in Hydroxyurea-Refractory Polycythemia Vera (ASH 2023)
HDM2 antagonist therapy represents a rational and highly effective treatment approach in PV. The durable effects of idasanutlin on phlebotomy requirements and splenomegaly persist even after treatment discontinuation. Additionally, the lack of appearance of TP53 mutations or loss of TP53 in those who progress suggest that the previously-described transient TP53 mutations do not have long-term clinical implications.
Clinical
|
TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
|
TP53 mutation • ASXL1 mutation • JAK2 V617F
|
idasanutlin (RG7388) • hydroxyurea
1year
Cebpβ/IL1/TNFα Positive Feedback Loop Drives Drug Resistance of BCL2 and MDM2 Inhibitors in Monocytic Leukemia Cells (ASH 2023)
In summary, we have described a positive feedback loop between CEBPB, IL-1/TNFα, and monocytic differentiation in monocytic leukemia that contributes to intrinsic and extrinsic drug resistance against BCL2 and MDM2 inhibitors. This crosstalk and the consequent drug resistance are further reinforced by venetoclax/MDM2 inhibition treatment. Combining venetoclax or idasanutlin with IL-1/TNFα antagonists or an IRAK inhibitor can abrogate the feedback loop and induce synergistic cytotoxic effects, offering promising therapeutic strategies to enhance the treatment efficacy of venetoclax and MDM2 inhibitors for monocytic leukemia.
IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • TNFA (Tumor Necrosis Factor-Alpha) • KLF4 (Kruppel-like factor 4) • IRF8 (Interferon Regulatory Factor 8) • CASP3 (Caspase 3) • BCL2A1 (BCL2 Related Protein A1) • SPI1 (Spi-1 Proto-Oncogene) • MAFB (MAF BZIP Transcription Factor B) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • CASP6 (Caspase 6, apoptosis-related cysteine peptidase) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • BBC3 (BCL2 Binding Component 3) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1) • JUNB (JunB Proto-Oncogene AP-1 Transcription Factor Subunit)
|
TP53 wild-type
|
Venclexta (venetoclax) • idasanutlin (RG7388)
1year
Navtemadlin, a Novel MDM2 Inhibitor, Potentiated Venetoclax-Induced Antitumor Efficacy in TP53 Wild-Type Acute Myeloid Leukemia (AML) (ASH 2023)
A proof-of-concept study with idasanutlin (idasa), a first-generation MDM2 inhibitor and ven demonstrated manageable safety and encouraging efficacy in relapsed/refractory AML patients (Daver et al. Nvtm, a potent second-generation MDM2 inhibitor, rapidly restored p53 function, induced apoptosis in p53WT AML MOLM-13 by impeding cell cycle, viability, clonogenicity potential, and reducing both glycolysis and oxidative phosphorylation. Nvtm combined with ven significantly enhanced these effects. Importantly, this combination blocked stromal cell-mediated (contact and soluble factors) cytoprotection.
Clinical • PARP Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IL6 (Interleukin 6)
|
TP53 mutation • TP53 wild-type • MCL1 expression • TP53 expression
|
Venclexta (venetoclax) • navtemadlin (KRT-232) • idasanutlin (RG7388)
1year
Idasanutlin and Navitoclax Induce a Synergistic p53-Dependent Apoptotic Cell Death in T-Cell Acute Lymphoblastic Leukemia (ASH 2023)
Venetoclax showed an additive benefit in 3 lines, but was only synergistic in 1 of 5 lines tested...We also evaluated ruxolitinib in combination with idasanutlin, as recent work has shown overlapping responses to inhibitors of Jak/Stat or Bcl-2 (Yuan et al...Idasanutlin and combination therapy samples clustered closely in PCA analysis, with p53 response a strongly-induced pathway, as expected. Our data suggest that the rational combination of idasanutlin and navitoclax is highly active against T-ALL, with greater synergic opportunity compared to other available idasanutlin combination treatments, through induction of a p53-dependent apoptotic cell death.
IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BCL2L1 (BCL2-like 1) • BCL2L2 (BCL2 Like 2)
|
TP53 wild-type • CDKN2A mutation • MYC expression • NOTCH mutation
|
Venclexta (venetoclax) • Jakafi (ruxolitinib) • navitoclax (ABT 263) • idasanutlin (RG7388)
1year
Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells. (PubMed, J Neurooncol)
Our study identifies the combination of entinostat with olaparib as a new potential therapeutic approach for MYC-driven Group 3 MB.
Journal • PARP Biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
MYC amplification
|
Lynparza (olaparib) • doxorubicin hydrochloride • Kisqali (ribociclib) • Xpovio (selinexor) • Partruvix (pamiparib) • idasanutlin (RG7388) • Jingzhuda (entinostat) • vinblastine
1year
NCT Neuro Master Match - N²M² (NOA-20) (clinicaltrials.gov)
P1/2, N=228, Completed, University Hospital Heidelberg | Recruiting --> Completed | N=350 --> 228 | Trial completion date: Sep 2024 --> Feb 2023 | Trial primary completion date: Sep 2023 --> Feb 2023
Trial completion • Enrollment change • Trial completion date • Trial primary completion date
|
BRAF (B-raf proto-oncogene)
|
Tecentriq (atezolizumab) • Ibrance (palbociclib) • Alecensa (alectinib) • Torisel (temsirolimus) • Erivedge (vismodegib) • idasanutlin (RG7388) • Apocept (asunercept)
over1year
Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway. (PubMed, Cancer Res)
Furthermore, activation of the unfolded protein response using tunicamycin and thapsigargin was sufficient to activate the ATF4/CHOP stress response axis and sensitize to nutlin-3. Finally, cell line and patient-derived xenograft models demonstrated combinatorial effects of treatment with idasanutlin and carfilzomib on liposarcoma growth in vivo. Finally, cell line and patient-derived xenograft models demonstrated combinatorial effects of treatment with idasanutlin and carfilzomib on liposarcoma growth in vivo. Together, these data indicate that targeting of the proteasome could improve the efficacy of MDM2 inhibitors in liposarcoma.
Journal
|
ATF4 (Activating Transcription Factor 4)
|
carfilzomib • idasanutlin (RG7388) • Nutlin-3
over1year
SF3B1 Mutations Are Associated with Resistance to Non-Genotoxic MDM2 Inhibition in Chronic Lymphocytic Leukemia. (PubMed, Int J Mol Sci)
The novel striking finding of this study was an independent link between SF3B1 mutational status and poor response to RG7388. Overall, SF3B1 mutations in CLL patient samples were associated with resistance to treatment with RG7388 ex vivo, and patients with the wild type for both SF3B1 and TP53 are more likely to benefit from treatment with MDM2 inhibitors.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
|
TP53 mutation • SF3B1 mutation • CD38 expression • CD38 overexpression
|
idasanutlin (RG7388)
over1year
MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation. (PubMed, Biomedicines)
While some MDM2 inhibitors have progressed to early phase clinical trials in GBM, their efficacy, alone and in combination, is yet to be confirmed. In this article, we present an overview of MDM2 inhibitors currently under preclinical and clinical investigation, with a specific focus on the drugs being assessed in ongoing clinical trials for GBM patients.
Review • Journal
|
TP53 wild-type
|
navtemadlin (KRT-232) • idasanutlin (RG7388) • brigimadlin (BI 907828) • ALRN-6924
over1year
New P1 trial
|
Xpovio (selinexor) • idasanutlin (RG7388)
over1year
miR-16-5p enhances sensitivity to RG7388 through targeting PPM1D expression (WIP1) in Childhood Acute Lymphoblastic Leukemia. (PubMed, Cancer Drug Resist)
This is the first study indicating the mechanistic importance of miR-16-5p overexpression in chALL and its inhibitory role in leukemia treatment when combined with the p53-Mdm2 antagonist, RG7388. These findings might be useful for researchers and clinicians to pave the way for better management of chALL.
Journal
|
MDM2 (E3 ubiquitin protein ligase) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • MIR16 (MicroRNA 16)
|
TP53 wild-type
|
idasanutlin (RG7388)
over1year
Idasanutlin, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma (clinicaltrials.gov)
P1/2, N=33, Active, not recruiting, Mayo Clinic | Trial completion date: May 2023 --> Dec 2023
Trial completion date • Combination therapy
|
Ninlaro (ixazomib) • idasanutlin (RG7388)
over1year
Trial completion date • Trial primary completion date • Combination therapy
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 wild-type
|
Venclexta (venetoclax) • cytarabine • cyclophosphamide • topotecan • idasanutlin (RG7388) • fludarabine IV
over1year
Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR. (PubMed, J Ovarian Res)
In a selection of 166 compounds we showed that inhibitors of ATR and WEE1 were cytotoxic against a panel of OCCC cell lines. These two drugs are already in other clinical trials, making them ideal candidates for treatment of OCCC.
Journal
|
ARID1A (AT-rich interaction domain 1A)
|
ARID1A mutation
|
adavosertib (AZD1775) • pictilisib (GDC-0941) • ceralasertib (AZD6738) • idasanutlin (RG7388) • saracatinib (AZD0530) • torkinib (PP242) • AZD4320
over1year
Combination Therapies Targeting Alk-Aberrant Neuroblastoma in Preclinical Models. (PubMed, Clin Cancer Res)
In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma.
Preclinical • Journal • Combination therapy
|
ALK (Anaplastic lymphoma kinase)
|
ALK mutation • ALK amplification
|
Lorbrena (lorlatinib) • doxorubicin hydrochloride • cyclophosphamide • vincristine • idasanutlin (RG7388)
almost2years
New ovarian cancer approach based on sensitizing the MDM2 inhibitor by an exportin-1 inhibitor (AACR 2023)
Our results confirmed that the combination treatment with RG-7388 (1M) and Selinexor (1M), which has never been investigated before for treating ovarian cancer cells, reduced the cell viability, upregulated apoptotic proteins, and induced cell death through activation of caspase-mediated apoptotic mechanisms.Grants: The Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida, provided the funds for this study.
IO biomarker
|
TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • XPO1 (Exportin 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
TP53 mutation • TP53 expression
|
Xpovio (selinexor) • idasanutlin (RG7388)
almost2years
Intracellular effects of blocking MDM2 and HMG-CoA reductase in metastatic prostate cancer cells (AACR 2023)
Furthermore, the scratch assay showed inhibition of migration of the PCa cells, particularly after the combination treatments. Our results have confirmed that RG7388, simvastatin, and their combination treatments can reverse EMT, inhibit migration, and reduce cancer stemness in p53 mutant prostate cancer cells.
Metastases
|
MDM2 (E3 ubiquitin protein ligase)
|
TP53 mutation
|
idasanutlin (RG7388)
almost2years
Splicing Modulation Results in Aberrant Isoforms and Protein Products of p53 Pathway Genes and the Sensitization of B Cells to Non-Genotoxic MDM2 Inhibition. (PubMed, Int J Mol Sci)
E7107 synergized with the MDM2 inhibitor RG7388, via dual MDM2 inhibition; by E7107 at the transcript level and by RG7388 at the protein level, producing greater p53 stabilisation and apoptosis. This study provides evidence for a synergistic MDM2 and spliceosome inhibitor combination as a novel approach to treat CLL and potentially other haematological malignancies.
Journal
|
CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
TP53 wild-type
|
idasanutlin (RG7388)
almost2years
Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation. (PubMed, NAR Cancer)
We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified idasanutlin-induced serum miRNA expression changes upon one day and 11 days of treatment. By limiting to miRNAs with a tumour-related induction, we put forward hsa-miR-34a-5p as a potential pharmacodynamic biomarker of p53 activation in serum.
Journal
|
MIR34A (MicroRNA 34a-5p)
|
Torisel (temsirolimus) • idasanutlin (RG7388)