PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33524216-11 2021 Nutlin-3 increased Notch signaling (NICD, Hes1) and DAPT inhibition of Notch activation prevented Nutlin-3 (p53)-induced asymmetric SC self-renewal divisions in aged keratinocytes. nutlin 3 98-106 tumor protein p53 Homo sapiens 108-111 32934219-7 2020 CDK9 inhibitor atuveciclib downregulated MDM4 and enhanced p53 activity induced by nutlin-3a, an inhibitor of p53-MDM2 interaction, and synergized with nutlin-3a in killing A375 melanoma cells. nutlin 3 83-92 tumor protein p53 Homo sapiens 59-62 32611259-8 2020 In addition, the C18-CAMEL/p53 plasmid complexes and the MDM2 inhibitor nutlin-3a showed significantly synergistic anticancer activity against MCF-7 cells expressing wild-type p53. nutlin 3 72-81 tumor protein p53 Homo sapiens 176-179 33303573-1 2021 In this study, we explored whether Nutlin-3a, a well-known nontoxic small-molecule compound antagonizing the inhibitory interaction of MDM2 with the tumor suppressor p53, may restore ligands for natural killer (NK) cell-activating receptors (NK-ARs) on neuroblastoma (NB) cells to enhance the NK cell-mediated killing. nutlin 3 35-44 tumor protein p53 Homo sapiens 166-169 32800832-9 2020 Overexpression of MDM2 ameliorated the inhibitory effect of FBXO31 on SiHa cells, while the MDM2/p53 axis-specific inhibitor Nutlin-3a facilitated this inhibitory effect. nutlin 3 125-134 tumor protein p53 Homo sapiens 97-100 32934219-7 2020 CDK9 inhibitor atuveciclib downregulated MDM4 and enhanced p53 activity induced by nutlin-3a, an inhibitor of p53-MDM2 interaction, and synergized with nutlin-3a in killing A375 melanoma cells. nutlin 3 83-92 tumor protein p53 Homo sapiens 110-113 32641480-17 2020 Fortunately, p53 phosphorylation can also be provided by drugs such as Nutlin-3, leading to synergistic reactivation of EBV. nutlin 3 71-79 tumor protein p53 Homo sapiens 13-16 32874188-9 2020 Isogenic HCT116 p53-wt/null cancer cells demonstrated that CD276 is induced on the cell surface by Nutlin-3 in a p53-dependent manner. nutlin 3 99-107 tumor protein p53 Homo sapiens 16-19 32874188-9 2020 Isogenic HCT116 p53-wt/null cancer cells demonstrated that CD276 is induced on the cell surface by Nutlin-3 in a p53-dependent manner. nutlin 3 99-107 tumor protein p53 Homo sapiens 113-116 32063580-7 2020 Our results demonstrate that Nutlin-3 but not RITA (reactivation of p53 and induction of tumor cell apoptosis) effectively disrupted the p53-MDM2-MDM4 complex to activate p53, which increased robustly with cisplatin/Nutlin-3 combination and enhanced antitumor effects more than either agent alone. nutlin 3 29-37 tumor protein p53 Homo sapiens 137-140 32664789-3 2020 Data from The Genomics of Drug Sensitivity in Cancer database showed that three drugs: (5Z)-7-oxozeaenol, dabrafenib and nutlin-3a (-), have shown more resistance in patients with TP53 mutation. nutlin 3 121-130 tumor protein p53 Homo sapiens 180-184 32063580-7 2020 Our results demonstrate that Nutlin-3 but not RITA (reactivation of p53 and induction of tumor cell apoptosis) effectively disrupted the p53-MDM2-MDM4 complex to activate p53, which increased robustly with cisplatin/Nutlin-3 combination and enhanced antitumor effects more than either agent alone. nutlin 3 29-37 tumor protein p53 Homo sapiens 137-140 31918545-2 2020 All the probes showed potent inhibitory and acceptable cell toxicity compared with commercially available p53-MDM2 inhibitor Nutlin-3, and can increase the protein expression level of p53 and MDM2 in A549 cell line, in particular, probe 10 and 11 can increase the protein expression level of p53 than nutlin-3. nutlin 3 125-133 tumor protein p53 Homo sapiens 106-109 31866490-7 2020 CDK9 inhibitors further showed synergistic effects in killing p53+/+ HCT116 cells when combined with the MDM2 inhibitor Nutlin-3. nutlin 3 120-128 tumor protein p53 Homo sapiens 62-65 31774938-7 2020 The most potent library member (Ki = 0.095 mum) identified is almost as active as Nutlin-3, a potent inhibitor of the p53-MDM2 PPI. nutlin 3 82-90 tumor protein p53 Homo sapiens 118-121 31918545-2 2020 All the probes showed potent inhibitory and acceptable cell toxicity compared with commercially available p53-MDM2 inhibitor Nutlin-3, and can increase the protein expression level of p53 and MDM2 in A549 cell line, in particular, probe 10 and 11 can increase the protein expression level of p53 than nutlin-3. nutlin 3 125-133 tumor protein p53 Homo sapiens 184-187 31918545-2 2020 All the probes showed potent inhibitory and acceptable cell toxicity compared with commercially available p53-MDM2 inhibitor Nutlin-3, and can increase the protein expression level of p53 and MDM2 in A549 cell line, in particular, probe 10 and 11 can increase the protein expression level of p53 than nutlin-3. nutlin 3 125-133 tumor protein p53 Homo sapiens 184-187 31720601-0 2019 The hydrophobically-tagged MDM2-p53 interaction inhibitor Nutlin-3a-HT is more potent against tumor cells than Nutlin-3a. nutlin 3 58-70 tumor protein p53 Homo sapiens 32-35 31691131-7 2020 In addition, nutlin-3 effectively abrogated the intracellular survival of mycobacteria in both TB patients and healthy controls after H37Ra infection for 24 h, indicating that the enhancement of p53 production effectively suppressed the intracellular survival of Mtb in hosts. nutlin 3 13-21 tumor protein p53 Homo sapiens 195-198 31767563-7 2020 Ex vivo Nutlin-3 (MDM2 inhibitor) treatment of blood and BM increased p53 and p21 expression in CTCs and DTCs compared with DMSO controls. nutlin 3 8-16 tumor protein p53 Homo sapiens 70-73 32280825-14 2020 Presence and activation of p53 are required for exertion of the radiosensitizing effect by nutlin-3, but this is not the sole determinant of the effect. nutlin 3 91-99 tumor protein p53 Homo sapiens 27-30 31720601-2 2019 Nutlin-3a-HT, created by fusing the hydrophobic tag HyT13 to the MDM2-p53 interaction inhibitor Nutlin-3a, prevented cellular accumulation of MDM2 upon p53 reactivation, and had a stronger effect on cell viability and the induction of apoptosis than Nutlin-3a. nutlin 3 0-12 tumor protein p53 Homo sapiens 70-73 31720601-2 2019 Nutlin-3a-HT, created by fusing the hydrophobic tag HyT13 to the MDM2-p53 interaction inhibitor Nutlin-3a, prevented cellular accumulation of MDM2 upon p53 reactivation, and had a stronger effect on cell viability and the induction of apoptosis than Nutlin-3a. nutlin 3 0-12 tumor protein p53 Homo sapiens 152-155 31134974-0 2019 Dual-channel surface plasmon resonance monitoring of intracellular levels of the p53-MDM2 complex and caspase-3 induced by MDM2 antagonist Nutlin-3. nutlin 3 139-147 tumor protein p53 Homo sapiens 81-84 31502598-7 2019 The feasibility of the method for the screening of the DNA-PK inhibitor and the inhibitor of p53-MDM2 interaction has been demonstrated and the half-maximal inhibitory concentration (IC50) values of wortmannin and Nutlin-3 (21 nM and 83 nM, respectively) were highly comparable with those obtained by other methods. nutlin 3 214-222 tumor protein p53 Homo sapiens 93-96 30389549-7 2019 Using primary samples from acute leukemia patients, we show that the combination of Nutlin-3 plus Tanshinone IIA synergistically induces cytotoxicity by activating p53 and inhibiting the AKT/mTOR pathway. nutlin 3 84-92 tumor protein p53 Homo sapiens 164-167 30966857-4 2019 Activation of p53 by treatment with either etoposide or the small-molecule MDM2 inhibitor nutlin 3A yields strikingly similar genome-wide binding of p53 and concomitant changes to local chromatin modifications and structure. nutlin 3 90-99 tumor protein p53 Homo sapiens 14-17 30966857-4 2019 Activation of p53 by treatment with either etoposide or the small-molecule MDM2 inhibitor nutlin 3A yields strikingly similar genome-wide binding of p53 and concomitant changes to local chromatin modifications and structure. nutlin 3 90-99 tumor protein p53 Homo sapiens 149-152 29803744-9 2018 Co-immunoprecipitation assay showed that SIRT1 could bind to p53, reduce its acetylation level, and treatment with nutlin-3A reversed the effect of SIRT1 on the level of p53 in ADSCs. nutlin 3 115-124 tumor protein p53 Homo sapiens 61-64 30096294-0 2018 PIM2 survival kinase is upregulated in a p53-dependent manner in cells treated with camptothecin or co-treated with actinomycin D and nutlin-3a. nutlin 3 134-143 tumor protein p53 Homo sapiens 41-44 29803744-9 2018 Co-immunoprecipitation assay showed that SIRT1 could bind to p53, reduce its acetylation level, and treatment with nutlin-3A reversed the effect of SIRT1 on the level of p53 in ADSCs. nutlin 3 115-124 tumor protein p53 Homo sapiens 170-173 30355102-7 2018 The interaction of MDM2 with p53 was disrupted by neuronal treatment with nutlin-3a. nutlin 3 74-83 tumor protein p53 Homo sapiens 29-32 29394130-3 2018 Wild-type p53 expressing HCT116 colon cancer cells were resistant to apoptosis in response to the MDM2 antagonist Nutlin-3a. nutlin 3 114-123 tumor protein p53 Homo sapiens 10-13 29842899-4 2018 To stimulate p53 in synergistic fashion, we exposed A549 lung cancer cells to actinomycin D and nutlin-3a (A + N). nutlin 3 96-105 tumor protein p53 Homo sapiens 13-16 29980405-8 2018 Furthermore, in some cases, cells with WT-TP53 were more sensitive to the combination of drugs and suboptimal doses of the MDM2 inhibitor nutlin-3a. nutlin 3 138-147 tumor protein p53 Homo sapiens 42-46 29141234-5 2017 We demonstrated that direct inactivation of p53 by SV40 large T antigen, a short hairpin RNA against Trp53, or genetic ablation of Trp53 in Dgcr8-/- PSCs enables neural differentiation, while activation of p53 by the MDM2 inhibitor nutlin-3a in wild-type ESCs inhibits neural differentiation. nutlin 3 232-241 tumor protein p53 Homo sapiens 44-47 28798402-3 2017 In this study, we show that treatment of various p53-defective bortezomib-resistant solid tumor cells with bortezomib plus nutlin-3 induces paraptosis, which is a cell death mode accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. nutlin 3 123-131 tumor protein p53 Homo sapiens 49-52 27626308-10 2016 GSK2830371 and the MDM2 inhibitor Nutlin-3a acted synergistically in p53 wild-type cells. nutlin 3 34-43 tumor protein p53 Homo sapiens 69-72 28416637-9 2017 To better probe the p53 response, SJSA cells (shCDK19 versus shCTRL) were treated with the p53 activator nutlin-3. nutlin 3 105-113 tumor protein p53 Homo sapiens 91-94 27813088-4 2017 In order to improve the selectivity of the HIMA for HUFs harbouring TP53 mutations, we explored the use of Nutlin-3a, an MDM2 inhibitor that leads to stabilisation and activation of wild-type (WT) p53. nutlin 3 107-116 tumor protein p53 Homo sapiens 197-200 28464864-2 2017 We then examined anti-tumor effects of metformin, an agent for type 2 diabetes, and combinatory effects of metformin and nutlin-3a, an inhibitor for ubiquitin-mediated p53 degradation, on human mesothelioma. nutlin 3 121-130 tumor protein p53 Homo sapiens 168-171 27177180-7 2017 Pharmacodynamic studies demonstrated that inhibition of cell growth following exposure to TMZ/nutlin3a correlated with: 1) activation of the p53 pathway, 2) downregulation of DNA repair proteins, 3) persistence of DNA damage, and 4) decreased invasion. nutlin 3 94-102 tumor protein p53 Homo sapiens 141-144 27556362-6 2016 Among the p53-positive ependymomas, the vast majority exhibited a RELA fusion leading to the hypothesis that p53 inactivation might be linked to RELA positivity.In order to assess the potential of p53 reactivation through MDM2 inhibition in ependymoma, we evaluated the effects of Actinomycin-D and Nutlin-3 treatment in two preclinical ependymoma models representing the high-risk subtypes PF-EPN-A and ST-EPN-RELA. nutlin 3 299-307 tumor protein p53 Homo sapiens 109-112 27556362-6 2016 Among the p53-positive ependymomas, the vast majority exhibited a RELA fusion leading to the hypothesis that p53 inactivation might be linked to RELA positivity.In order to assess the potential of p53 reactivation through MDM2 inhibition in ependymoma, we evaluated the effects of Actinomycin-D and Nutlin-3 treatment in two preclinical ependymoma models representing the high-risk subtypes PF-EPN-A and ST-EPN-RELA. nutlin 3 299-307 tumor protein p53 Homo sapiens 109-112 24921920-2 2014 Nutlin-3, an MDM2-p53 antagonist, has previously been reported to be a competitive MDR-1 inhibitor. nutlin 3 0-8 tumor protein p53 Homo sapiens 18-21 26431163-6 2015 We pretreated such cells with Nutlin-3a, a prototype inhibitor of the p53-antagonist Mdm2. nutlin 3 30-39 tumor protein p53 Homo sapiens 70-73 24926617-2 2014 To investigate post-transcriptional controls as an additional dimension of p53-directed gene expression responses, we performed a translatome analysis through polysomal profiling on MCF7 cells upon 16 hours of doxorubicin or nutlin-3a treatment. nutlin 3 225-234 tumor protein p53 Homo sapiens 75-78 27547448-7 2016 Consistent with the inhibitory effect of PXR on p53, elevated PXR levels decreased doxorubicin- or nutlin-3a-mediated toxicity and promoted malignant transformation in colon cancer cells. nutlin 3 99-108 tumor protein p53 Homo sapiens 48-51 26556313-7 2016 Supportively, molecular docking studies revealed considerable homology in the docking mode of G613 and the known Mdm2 inhibitor Nutlin-3, to p53 binding pocket of Mdm2. nutlin 3 128-136 tumor protein p53 Homo sapiens 141-144 26158294-9 2015 Treatment with nutlin-3a or etoposide induced CST5 in a p53-dependent manner. nutlin 3 15-24 tumor protein p53 Homo sapiens 56-59 25483068-2 2015 Using genome-wide shRNA screening, we recently identified the ATM kinase as synthetic lethal with Nutlin-3, an MDM2 inhibitor that leads to non-genotoxic p53 activation. nutlin 3 98-106 tumor protein p53 Homo sapiens 154-157 24867259-4 2014 We report on how nutlin-3-stimulated ERK1/2 activity inhibits p53-induced apoptosis. nutlin 3 17-25 tumor protein p53 Homo sapiens 62-65 24867259-12 2014 Collectively, these results suggest that nutlin-3-activated ERK1/2 may stimulate the transcription of BCL2A1 via the activation of ELK1, and BCL2A1 expression may contribute to the inhibitory effect of ERK1/2 on nutlin-3-induced apoptosis, thereby constituting a negative feedback loop of p53-induced apoptosis. nutlin 3 41-49 tumor protein p53 Homo sapiens 289-292 24270847-2 2013 Using Brownian dynamics simulations, we show that the preferential binding of the MDM2 protein to the geometrical isomers of Nutlin-3, an effective anticancer lead that works by inhibiting the interaction between the proteins p53 and MDM2, can be explained by kinetic arguments related to the formation of the MDM2:Nutlin-3 encounter complex. nutlin 3 125-133 tumor protein p53 Homo sapiens 226-229 24522962-3 2014 Here, we describe inhibition experiments on p53/Mdm2 interaction in Trichoplax adhaerens by applying the inhibitors nutlin-3 and roscovitine. nutlin 3 116-124 tumor protein p53 Homo sapiens 44-47 24366007-8 2014 Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-mu, an inhibitor of the mitochondrial translocation of p53. nutlin 3 23-31 tumor protein p53 Homo sapiens 100-103 24366007-8 2014 Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-mu, an inhibitor of the mitochondrial translocation of p53. nutlin 3 23-31 tumor protein p53 Homo sapiens 199-202 24366007-11 2014 Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis. nutlin 3 41-49 tumor protein p53 Homo sapiens 144-147 24366007-11 2014 Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis. nutlin 3 41-49 tumor protein p53 Homo sapiens 362-365 24473562-2 2014 Therefore, the objective of the present study was to evaluate the in vitro effect of treatment with Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, on the expression of the suppressor of cytokine signaling 1 in primary acute myeloid leukemia cells and in myeloid cell lines with differential p53 status. nutlin 3 100-108 tumor protein p53 Homo sapiens 149-152 24473562-2 2014 Therefore, the objective of the present study was to evaluate the in vitro effect of treatment with Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, on the expression of the suppressor of cytokine signaling 1 in primary acute myeloid leukemia cells and in myeloid cell lines with differential p53 status. nutlin 3 100-108 tumor protein p53 Homo sapiens 310-313 24268795-3 2014 Seven compounds showed an antiproliferative profile superior to the p53-MDM2 interaction inhibitor nutlin-3, and induced cell death by apoptosis. nutlin 3 99-107 tumor protein p53 Homo sapiens 68-71 24270847-2 2013 Using Brownian dynamics simulations, we show that the preferential binding of the MDM2 protein to the geometrical isomers of Nutlin-3, an effective anticancer lead that works by inhibiting the interaction between the proteins p53 and MDM2, can be explained by kinetic arguments related to the formation of the MDM2:Nutlin-3 encounter complex. nutlin 3 315-323 tumor protein p53 Homo sapiens 226-229 24231949-5 2013 Here, we have reviewed existing cyclotherapy regimens using two well-known p53 activators, nutlin-3 and actinomycin D. nutlin 3 91-99 tumor protein p53 Homo sapiens 75-78 23187459-3 2013 Combined treatment with nutlin-3 and TRAIL markedly induces apoptosis in HCT116 cells (p53 wild type), but not in HCT116 p53-/- cells, suggesting that p53 is critical for the sensitizing effect of nutlin-3 on TRAIL-induced apoptosis. nutlin 3 24-32 tumor protein p53 Homo sapiens 87-90 24127627-1 2013 Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. nutlin 3 184-192 tumor protein p53 Homo sapiens 239-242 23812671-8 2013 Suppression of p53 in melanoma cells abrogated Nt-3"s effects fully and vemurafenib"s effects partially. nutlin 3 47-51 tumor protein p53 Homo sapiens 15-18 23720736-7 2013 RUNX2 protein levels decrease upon stabilization of p53 with the MDM2 inhibitor Nutlin-3. nutlin 3 80-88 tumor protein p53 Homo sapiens 52-55 23398638-7 2013 The role of MDM2 binding was explored by inhibiting MDM2/p53 binding with nutlin-3. nutlin 3 74-82 tumor protein p53 Homo sapiens 57-60 23054209-1 2013 The effect of Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, was investigated on the steady-state mRNA levels of the transcription factors E2F1 and E2F7 in a cohort of primary B-chronic lymphocytic leukemia (B-CLL) patient samples (n = 15) and normal peripheral blood mononuclear cells (PBMC). nutlin 3 14-22 tumor protein p53 Homo sapiens 63-66 23187804-0 2012 p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3. nutlin 3 91-99 tumor protein p53 Homo sapiens 0-3 22469985-3 2013 We have reported that p53 reactivation by an inhibitor of the p53-MDM2 interaction, Nutlin-3, induces selective and massive apoptosis in PEL cells leading to efficient anti-tumor activity in a subcutaneous xenograft model for PEL. nutlin 3 84-92 tumor protein p53 Homo sapiens 22-25 22469985-3 2013 We have reported that p53 reactivation by an inhibitor of the p53-MDM2 interaction, Nutlin-3, induces selective and massive apoptosis in PEL cells leading to efficient anti-tumor activity in a subcutaneous xenograft model for PEL. nutlin 3 84-92 tumor protein p53 Homo sapiens 62-65 22469985-5 2013 Interestingly, our results demonstrate that spontaneous induction of viral lytic replication in tumors could drastically attenuate the p53-dependent apoptotic response to Nutlin-3. nutlin 3 171-179 tumor protein p53 Homo sapiens 135-138 24154492-4 2013 With this approach, we visualize the p53-HDM2 interaction in living cells and directly monitor the disruption of this interaction by Nutlin 3, a drug developed to boost p53 activity in cancer therapy. nutlin 3 133-141 tumor protein p53 Homo sapiens 37-40 24154492-4 2013 With this approach, we visualize the p53-HDM2 interaction in living cells and directly monitor the disruption of this interaction by Nutlin 3, a drug developed to boost p53 activity in cancer therapy. nutlin 3 133-141 tumor protein p53 Homo sapiens 169-172 21725357-0 2012 MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63. nutlin 3 58-66 tumor protein p53 Homo sapiens 42-45 22785205-5 2012 In this study, we tested if combining Inauhzin with Nutlin-3, an inhibitor of MDM2-p53 binding, might synergistically activate p53 to suppress tumor growth. nutlin 3 52-60 tumor protein p53 Homo sapiens 83-86 22785205-5 2012 In this study, we tested if combining Inauhzin with Nutlin-3, an inhibitor of MDM2-p53 binding, might synergistically activate p53 to suppress tumor growth. nutlin 3 52-60 tumor protein p53 Homo sapiens 127-130 22830357-6 2012 In accordance with this hypothesis, etoposide or nutlin-3 treatment or a small interfering RNA (siRNA) against BCL6 (B-cell lymphoma 6) inhibited the proliferation of DoHH2 cells by up-regulating p53 without affecting either miR-34a or c-MYC levels. nutlin 3 49-57 tumor protein p53 Homo sapiens 196-199 22064349-0 2012 Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia. nutlin 3 69-77 tumor protein p53 Homo sapiens 25-28 22064349-2 2012 We hypothesized that co-inhibition of MDM2 and HDACs, with nutlin-3 and valproic acid (VPA) would additively inhibit growth in leukemic cells expressing wild type TP53 and induce p53-mediated apoptosis. nutlin 3 59-67 tumor protein p53 Homo sapiens 163-167 22064349-2 2012 We hypothesized that co-inhibition of MDM2 and HDACs, with nutlin-3 and valproic acid (VPA) would additively inhibit growth in leukemic cells expressing wild type TP53 and induce p53-mediated apoptosis. nutlin 3 59-67 tumor protein p53 Homo sapiens 179-182 22948151-6 2012 Induction of p53 can be achieved by several means, such as UV radiation and treatment with anti-cancer agents (including doxorubicin, etoposide, roscovitine, flavopiridol, and nutlin-3). nutlin 3 176-184 tumor protein p53 Homo sapiens 13-16 22260869-4 2012 Likewise, expression of either p53DD or knockdown of p53 prevented caspase-3/7 activation and chromatin fragmentation induced by nutlin-3, a compound that prevents the interaction between p53 and the E3 ubiquitin ligase MDM2. nutlin 3 129-137 tumor protein p53 Homo sapiens 31-34 22260869-4 2012 Likewise, expression of either p53DD or knockdown of p53 prevented caspase-3/7 activation and chromatin fragmentation induced by nutlin-3, a compound that prevents the interaction between p53 and the E3 ubiquitin ligase MDM2. nutlin 3 129-137 tumor protein p53 Homo sapiens 53-56 22044530-6 2011 In the presence of nutlin-3, an HDM2 inhibitor, TCDD was still able to suppress 1-NP-induced p53 expression. nutlin 3 19-27 tumor protein p53 Homo sapiens 93-96 22233735-4 2012 METHODS: We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14Arf and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. nutlin 3 191-199 tumor protein p53 Homo sapiens 211-214 21796156-4 2011 We previously showed that nutlin-3, an antagonist of MDM2, activates the p53 pathway in BL cell lines harboring wild-type p53. nutlin 3 26-34 tumor protein p53 Homo sapiens 73-76 21796156-4 2011 We previously showed that nutlin-3, an antagonist of MDM2, activates the p53 pathway in BL cell lines harboring wild-type p53. nutlin 3 26-34 tumor protein p53 Homo sapiens 122-125 21068437-5 2011 Pharmacologic inhibition of p53 rescued the erythroid defect, whereas nutlin-3, a compound that activates p53 through inhibition of HDM2, selectively impaired erythropoiesis. nutlin 3 70-78 tumor protein p53 Homo sapiens 106-109 21460101-0 2011 Functional analysis of the p53 pathway in neuroblastoma cells using the small-molecule MDM2 antagonist nutlin-3. nutlin 3 103-111 tumor protein p53 Homo sapiens 27-30 21386967-5 2011 Direct or indirect activation of TP53 pathway with 5-aza-2"-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells. nutlin 3 87-95 tumor protein p53 Homo sapiens 33-37 21159614-9 2010 Collectively, these results show that nutlin-3 may be a useful agent in combination with TRAIL and, importantly, uncover a novel regulatory effect of p53 on the expression of Mcl-1 in melanoma cells on treatment with nutlin-3, which may antagonize the therapeutic efficacy of other chemotherapeutic drugs in addition to docetaxel in melanoma. nutlin 3 217-225 tumor protein p53 Homo sapiens 150-153 21106726-1 2011 PURPOSE: To analyze the effect of the combination of Dasatinib, a multikinase inhibitor, plus Nutlin-3, a nongenotoxic activator of the p53 pathway, in primary B chronic lymphocytic leukemia (B-CLL) patient samples and B leukemic cell line models. nutlin 3 94-102 tumor protein p53 Homo sapiens 136-139 22708054-0 2011 Catalytic, Enantioselective Synthesis of Stilbene cis-Diamines: A Concise Preparation of (-)-Nutlin-3, a Potent p53/MDM2 Inhibitor. nutlin 3 89-101 tumor protein p53 Homo sapiens 112-115 22708054-3 2011 This method then became the lynchpin for an enantioselective synthesis of (-)-Nutlin-3 (Hoffmann-LaRoche), a potent cis-imidazoline small molecule inhibitor of p53-MDM2 used extensively as a probe of cell biology and currently in drug development. nutlin 3 74-86 tumor protein p53 Homo sapiens 160-163 21173028-9 2011 Altogether, our data uncover a novel mechanism linking MYCN to apoptosis that can be triggered by the p53-reactivating compound Nutlin-3, supporting its use in the most difficult-to-treat subset of neuroblastoma. nutlin 3 128-136 tumor protein p53 Homo sapiens 102-105 20850924-3 2010 In the bortezomib sensitive wild-type TP53 MCL cells, the Nutlin-3/bortezomib combination caused G0/G1 cell cycle arrest followed by the increase in apoptosis induction. nutlin 3 58-66 tumor protein p53 Homo sapiens 38-42 21149449-7 2011 Consistent with the ability of Ski to inactivate p53, overexpressing Ski desensitized cells to genotoxic drugs and Nutlin-3, a small-molecule antagonist of Mdm2 that stabilizes p53 and activates the p53 pathway, whereas knocking down Ski increased the cellular sensitivity to these agents. nutlin 3 115-123 tumor protein p53 Homo sapiens 49-52 21149449-7 2011 Consistent with the ability of Ski to inactivate p53, overexpressing Ski desensitized cells to genotoxic drugs and Nutlin-3, a small-molecule antagonist of Mdm2 that stabilizes p53 and activates the p53 pathway, whereas knocking down Ski increased the cellular sensitivity to these agents. nutlin 3 115-123 tumor protein p53 Homo sapiens 177-180 21149449-7 2011 Consistent with the ability of Ski to inactivate p53, overexpressing Ski desensitized cells to genotoxic drugs and Nutlin-3, a small-molecule antagonist of Mdm2 that stabilizes p53 and activates the p53 pathway, whereas knocking down Ski increased the cellular sensitivity to these agents. nutlin 3 115-123 tumor protein p53 Homo sapiens 177-180 19421231-4 2009 We show here that nutlin-3, a potent antagonist of MDM2, activates the p53 pathway in all BL cell lines harboring wild-type p53, regardless of EBV status. nutlin 3 18-26 tumor protein p53 Homo sapiens 71-74 20305378-0 2010 Inactivation of p53 signaling by p73 or PTEN ablation results in a transformed phenotype that remains susceptible to Nutlin-3 mediated apoptosis. nutlin 3 117-125 tumor protein p53 Homo sapiens 16-19 20215548-5 2010 Knocking down p53 attenuated the effect of Nutlin-3 on DEK expression, whereas knocking down DEK significantly increased both spontaneous and Nutlin-3-induced apoptosis. nutlin 3 43-51 tumor protein p53 Homo sapiens 14-17 20178585-3 2010 The aim of this study was to selectively kill p53 deficient cells (FaDu and H1299) by taxol and to protect p53 wild type cells (A549) by the prior administration of nutlin-3 in comparison to certain known anticancer drugs (5-fluorouracil, camptothecin, roscovitine). nutlin 3 165-173 tumor protein p53 Homo sapiens 107-110 20157557-0 2009 Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3. nutlin 3 103-111 tumor protein p53 Homo sapiens 40-43 19421231-9 2009 Most BL patients with wild-type p53 tumors could therefore benefit from treatment with nutlin-3, after a careful determination of the latency pattern of EBV in infected patients. nutlin 3 87-95 tumor protein p53 Homo sapiens 32-35 20422343-5 2010 To investigate their effects in combination, a p53-mutant cholangiocarcinoma line HuCCT1 was treated with Nutlin-3 and/or gemcitabine in the current study. nutlin 3 106-114 tumor protein p53 Homo sapiens 47-50 19788889-7 2010 Although the HCT116 colon cancer cells did not mount a significant DNA damage response following Nutlin-3 treatment, Nutlin-3 enhanced the DNA damage response to the nucleotide synthesis inhibitor hydroxyurea in a p53-dependent manner. nutlin 3 117-125 tumor protein p53 Homo sapiens 214-217 19421231-4 2009 We show here that nutlin-3, a potent antagonist of MDM2, activates the p53 pathway in all BL cell lines harboring wild-type p53, regardless of EBV status. nutlin 3 18-26 tumor protein p53 Homo sapiens 124-127 19638586-4 2009 We show that, along with p53 reactivation, the proapoptotic p53-activator HIPK2 is degraded by MDM2 in Nutlin-3-treated cells, but activated by transiently reduced MDM2 levels in RITA-treated ones. nutlin 3 103-111 tumor protein p53 Homo sapiens 25-28 19638586-4 2009 We show that, along with p53 reactivation, the proapoptotic p53-activator HIPK2 is degraded by MDM2 in Nutlin-3-treated cells, but activated by transiently reduced MDM2 levels in RITA-treated ones. nutlin 3 103-111 tumor protein p53 Homo sapiens 60-63 19509161-0 2009 Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells. nutlin 3 30-38 tumor protein p53 Homo sapiens 15-18 19519319-1 2009 By analyzing the cDNA obtained from 16 B-cell chronic lymphocytic leukemia (B-CLL) patient samples, we found that Nutlin-3, a small molecule inhibitor of MDM2/p53 interaction, induced a characteristic gene expression profile (GEP) signature in 13 out of 16 B-CLL samples. nutlin 3 114-122 tumor protein p53 Homo sapiens 159-162 19188164-12 2009 CONCLUSION: These findings suggest that the MDM2 antagonist Nutlin-3 may be an effective agent in the treatment of MCL with or without wt-TP53. nutlin 3 60-68 tumor protein p53 Homo sapiens 138-142 19190243-8 2009 Therefore, therapeutic combinations of Nutlin-3 + gamma-secretase inhibitors might potentiate the cytotoxicity of Nutlin-3 in p53(wild-type) leukemic cells. nutlin 3 39-47 tumor protein p53 Homo sapiens 126-129 18779328-5 2008 In addition, STX6 can be induced by DNA damage and Mdm2 inhibitor Nutlin-3 in a p53-dependent manner. nutlin 3 66-74 tumor protein p53 Homo sapiens 80-83 18646312-6 2008 Strikingly, the p53 G1 checkpoint in G/G cells was activated by Nutlin-3 but not by etoposide, whereas in other Mdm2-overexpressing cells, both drugs activated p53 and subsequent G1 arrest or apoptosis. nutlin 3 64-72 tumor protein p53 Homo sapiens 16-19 18971636-11 2008 This regulation is observed in a transgenic p53-inducible cell system as well as in cells with wild-type p53 treated with nutlin-3, doxorubicin or paclitaxel. nutlin 3 122-130 tumor protein p53 Homo sapiens 44-47 18971636-11 2008 This regulation is observed in a transgenic p53-inducible cell system as well as in cells with wild-type p53 treated with nutlin-3, doxorubicin or paclitaxel. nutlin 3 122-130 tumor protein p53 Homo sapiens 105-108 18625847-5 2008 Rather, p53 accumulation by either knockdown of Mdm2 or addition of an Mdm2 inhibitor, Nutlin-3, before irradiation strongly attenuated the UV-induced DDR and increased cell survival. nutlin 3 87-95 tumor protein p53 Homo sapiens 8-11 18677110-1 2008 The cellular response to Nutlin-3, a small-molecule inhibitor of the p53 repressor MDM2, varies widely among human cancer-derived cell types. nutlin 3 25-33 tumor protein p53 Homo sapiens 69-72 18092340-5 2008 Analysis of the gene expression profile of the p53-transcriptional targets showed distinct features between chlorambucil, Nutlin-3 and fludarabine, which likely account for their differential effect on cell cycle in SKW6.4 cells. nutlin 3 122-130 tumor protein p53 Homo sapiens 47-50 17942917-5 2007 Using this transformation model, we examined the sensitivity of the D1/CDK-expressing cells to Nutlin-3, an HDM2 antagonist that activates p53. nutlin 3 95-103 tumor protein p53 Homo sapiens 139-142 17897804-2 2007 The imidazoline compound (Nutlin-3) is a promising small molecule antagonist of the MDM2-p53 interaction. nutlin 3 26-34 tumor protein p53 Homo sapiens 89-92 17709487-10 2007 The effects of RSV infection are antagonized by Nutlin-3, a specific chemical inhibitor that prevents the Mdm2/p53 association. nutlin 3 48-56 tumor protein p53 Homo sapiens 111-114 17504227-1 2007 To potentiate the response of acute myeloid leukemia (AML) to TRAIL cytotoxicity, we have adopted a strategy of combining nutlin-3, a potent non-genotoxic activator of the p53 pathway, with recombinant TRAIL. nutlin 3 122-130 tumor protein p53 Homo sapiens 172-175 17146434-6 2007 In the human dedifferentiated liposarcoma cell line (LS141) and the p53 wild-type HCT116 cells, Nutlin-3a induced downregulation of E2F1 and this effect appeared to be proteasome dependent. nutlin 3 96-105 tumor protein p53 Homo sapiens 68-71 17504227-6 2007 Moreover, while nutlin-3 up-regulated the expression of cyclin dependent kinase inhibitor p21, a p53-target gene mediating cell cycle block and showing anti-apoptotic activity, the simultaneous addition of TRAIL plus nutlin-3 induced the caspase-dependent cleavage of p21. nutlin 3 16-24 tumor protein p53 Homo sapiens 97-100 34485982-6 2021 Pharmacological-mediated increase of P53 protein levels with the Mdm2 inhibitor Nutlin-3a during early (mesoderm to cardiac mesoderm) stages of cardiogenesis resulted in a sizeable loss of cardiomyocytes due to increased apoptosis and cell cycle arrest. nutlin 3 80-89 tumor protein p53 Homo sapiens 37-40 17364023-5 2007 Our results demonstrated that the KSHV latency-associated nuclear antigen (LANA) bound to both p53 and MDM2 and that the MDM2 inhibitor Nutlin-3a disrupted the p53-MDM2-LANA complex and selectively induced massive apoptosis in PEL cells. nutlin 3 136-145 tumor protein p53 Homo sapiens 160-163 33794285-0 2021 Effect of pharmacodynamical interaction between nutlin-3a and aspirin in the activation of p53. nutlin 3 48-57 tumor protein p53 Homo sapiens 91-94 33794285-4 2021 In the presented work, we have aimed to investigate the effect of pharmacodynamical interaction between two anti-cancer drugs, nutlin-3a and aspirin in the activation of p53 protein. nutlin 3 127-136 tumor protein p53 Homo sapiens 170-173 17138942-4 2007 Although nutlin-3 and doxorubicin induced a comparable p53 accumulation in endothelial cells, nutlin-3 was significantly more efficient than doxorubicin in upregulating the p53 target genes CDKN1A/p21, MDM2, and GDF-15, as well as in inhibiting cell cycle progression. nutlin 3 9-17 tumor protein p53 Homo sapiens 55-58 17079445-6 2006 The sequential treatment with nutlin-3 alone, followed by transient exposure to nutlin-3 plus gemcitabine, efficiently compromised the clonogenicity of tumor cells with deletions or mutations of p53 but largely spared the proliferation of nontransformed human keratinocytes. nutlin 3 30-38 tumor protein p53 Homo sapiens 195-198 17079445-6 2006 The sequential treatment with nutlin-3 alone, followed by transient exposure to nutlin-3 plus gemcitabine, efficiently compromised the clonogenicity of tumor cells with deletions or mutations of p53 but largely spared the proliferation of nontransformed human keratinocytes. nutlin 3 80-88 tumor protein p53 Homo sapiens 195-198 16778203-8 2006 Furthermore, we provided evidence that inhibition of protein methyltransferases, especially arginine methyltransferases, relieve the repression of ECT2 induced by DNA damage or Nutlin-3 in a p53-dependent manner. nutlin 3 177-185 tumor protein p53 Homo sapiens 191-194 35429966-5 2022 In addition, we observed that Triptolide and Nutlin-3a were also cooperative in part of p53 deficient cases. nutlin 3 45-54 tumor protein p53 Homo sapiens 88-91 35410287-4 2022 RESULTS: By combining single-cell imaging and mathematical modeling of dose-dependent p53 dynamics induced by three chemotherapeutics of distinct mechanism-of-actions, including Etoposide, Nutlin-3a and 5-fluorouracil, and in five cancer cell types, we uncovered novel and highly variable p53 dynamic responses, in particular p53 transitional dynamics induced at intermediate drug concentrations, and identified the functional roles of distinct positive and negative feedback motifs of the p53 pathway in modulating the central p53-Mdm2 negative feedback to generate stimulus- and cell type-specific signaling responses. nutlin 3 189-198 tumor protein p53 Homo sapiens 86-89 35410287-4 2022 RESULTS: By combining single-cell imaging and mathematical modeling of dose-dependent p53 dynamics induced by three chemotherapeutics of distinct mechanism-of-actions, including Etoposide, Nutlin-3a and 5-fluorouracil, and in five cancer cell types, we uncovered novel and highly variable p53 dynamic responses, in particular p53 transitional dynamics induced at intermediate drug concentrations, and identified the functional roles of distinct positive and negative feedback motifs of the p53 pathway in modulating the central p53-Mdm2 negative feedback to generate stimulus- and cell type-specific signaling responses. nutlin 3 189-198 tumor protein p53 Homo sapiens 289-292 35410287-4 2022 RESULTS: By combining single-cell imaging and mathematical modeling of dose-dependent p53 dynamics induced by three chemotherapeutics of distinct mechanism-of-actions, including Etoposide, Nutlin-3a and 5-fluorouracil, and in five cancer cell types, we uncovered novel and highly variable p53 dynamic responses, in particular p53 transitional dynamics induced at intermediate drug concentrations, and identified the functional roles of distinct positive and negative feedback motifs of the p53 pathway in modulating the central p53-Mdm2 negative feedback to generate stimulus- and cell type-specific signaling responses. nutlin 3 189-198 tumor protein p53 Homo sapiens 326-329 35410287-4 2022 RESULTS: By combining single-cell imaging and mathematical modeling of dose-dependent p53 dynamics induced by three chemotherapeutics of distinct mechanism-of-actions, including Etoposide, Nutlin-3a and 5-fluorouracil, and in five cancer cell types, we uncovered novel and highly variable p53 dynamic responses, in particular p53 transitional dynamics induced at intermediate drug concentrations, and identified the functional roles of distinct positive and negative feedback motifs of the p53 pathway in modulating the central p53-Mdm2 negative feedback to generate stimulus- and cell type-specific signaling responses. nutlin 3 189-198 tumor protein p53 Homo sapiens 490-493 35410287-4 2022 RESULTS: By combining single-cell imaging and mathematical modeling of dose-dependent p53 dynamics induced by three chemotherapeutics of distinct mechanism-of-actions, including Etoposide, Nutlin-3a and 5-fluorouracil, and in five cancer cell types, we uncovered novel and highly variable p53 dynamic responses, in particular p53 transitional dynamics induced at intermediate drug concentrations, and identified the functional roles of distinct positive and negative feedback motifs of the p53 pathway in modulating the central p53-Mdm2 negative feedback to generate stimulus- and cell type-specific signaling responses. nutlin 3 189-198 tumor protein p53 Homo sapiens 528-531