675576-98-4 | 4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone

Packsize	Purity	Availability	Price	Discounted Price
1mg	97%	in stock	$120.00	$84.00
5mg	97%	in stock	$144.00	$101.00
25mg	97%	in stock	$639.00	$448.00
50mg	97%	in stock	$932.00	$652.00

Description

• Catalog Number: AB53663
• Chemical Name: 4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone
• CAS Number: 675576-98-4
• Molecular Formula: C30H30Cl2N4O4
• Molecular Weight: 581.4896
• MDL Number: MFCD14636430
• SMILES: COc1ccc(c(c1)OC(C)C)C1=N[C@H]([C@H](N1C(=O)N1CCNC(=O)C1)c1ccc(cc1)Cl)c1ccc(cc1)Cl

Computed Properties

• Complexity: 919
• Covalently-Bonded Unit Count: 1
• Defined Atom Stereocenter Count: 2
• Heavy Atom Count: 40
• Hydrogen Bond Acceptor Count: 5
• Hydrogen Bond Donor Count: 1
• Rotatable Bond Count: 6
• XLogP3: 5.2

Literature

• p53 and NF-κB coregulate proinflammatory gene responses in human macrophages.

  Cancer research 20140415

• Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma.

  Molecular cancer 20140101

• Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.

  ACS medicinal chemistry letters 20130509

• SOCS1 is significantly up-regulated in Nutlin-3-treated p53wild-type B chronic lymphocytic leukemia (B-CLL) samples and shows an inverse correlation with miR-155.

  Investigational new drugs 20121201

• An iTRAQ proteomics screen reveals the effects of the MDM2 binding ligand Nutlin-3 on cellular proteostasis.

  Journal of proteome research 20121102

• The sorafenib plus nutlin-3 combination promotes synergistic cytotoxicity in acute myeloid leukemic cells irrespectively of FLT3 and p53 status.

  Haematologica 20121101

• DNA damage response by single-strand breaks in terminally differentiated muscle cells and the control of muscle integrity.

  Cell death and differentiation 20121101

• A novel combination therapy approach for the treatment of acute myeloid leukemia: the multi-kinase inhibitor sorafenib and the HDM2 inhibitor nutlin-3.

  Haematologica 20121101

• Discovery of novel dihydroimidazothiazole derivatives as p53-MDM2 protein-protein interaction inhibitors: synthesis, biological evaluation and structure-activity relationships.

  Bioorganic & medicinal chemistry letters 20121015

• Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-α 2a specifically targets JAK2V617F-positive polycythemia vera cells.

  Blood 20121011

• Structure-activity relationship and antitumor activity of thio-benzodiazepines as p53-MDM2 protein-protein interaction inhibitors.

  European journal of medicinal chemistry 20121001

• Differential regulation of p21 (waf1) protein half-life by DNA damage and Nutlin-3 in p53 wild-type tumors and its therapeutic implications.

  Cancer biology & therapy 20120901

• A novel function of p53: a gatekeeper of retinal detachment.

  The American journal of pathology 20120901

• Ras homolog gene family, member A promotes p53 degradation and vascular endothelial growth factor-dependent angiogenesis through an interaction with murine double minute 2 under hypoxic conditions.

  Cancer 20120901

• Competitive binding between dynamic p53 transactivation subdomains to human MDM2 protein: implications for regulating the p53·MDM2/MDMX interaction.

  The Journal of biological chemistry 20120831

• MDM2 overexpression deregulates the transcriptional control of RB/E2F leading to DNA methyltransferase 3A overexpression in lung cancer.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120815

• Nutlin-3 differentially modulates miRNA34a and miRNA181 versus miR26a and miR155 in p53 proficient and p53 deficient B chronic lymphocytic leukemia (B-CLL) samples.

  Investigational new drugs 20120801

• The tumour suppressor p53 is frequently nonfunctional in Sézary syndrome.

  The British journal of dermatology 20120801

• Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth.

  Cancer biology & therapy 20120801

• The over-expression of miR-34a fails to block DoHH2 lymphoma cell proliferation by reducing p53 via c-MYC down-regulation.

  Nucleic acid therapeutics 20120801

• Integrin α5β1 plays a critical role in resistance to temozolomide by interfering with the p53 pathway in high-grade glioma.

  Cancer research 20120715

• Pharmacological activation of the p53 pathway by nutlin-3 exerts anti-tumoral effects in medulloblastomas.

  Neuro-oncology 20120701

• ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53.

  Nature chemical biology 20120701

• The histone acetyltransferase PCAF regulates p21 transcription through stress-induced acetylation of histone H3.

  Cell cycle (Georgetown, Tex.) 20120701

• Comparison of the antitumor effects of an MDM2 inhibitor, nutlin-3, in feline lymphoma cell lines with or without p53 mutation.

  Veterinary immunology and immunopathology 20120630

• Structure-based design of novel inhibitors of the MDM2-p53 interaction.

  Journal of medicinal chemistry 20120614

• Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor.

  Oncogene 20120607

• Chk2 mediates RITA-induced apoptosis.

  Cell death and differentiation 20120601

• Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signaling pathway in human melanocytes.

  Molecular cancer research : MCR 20120601

• The central valine concept provides an entry in a new class of non peptide inhibitors of the p53-MDM2 interaction.

  Bioorganic & medicinal chemistry letters 20120515

• Pharmacological inhibition of Mdm2 triggers growth arrest and promotes DNA breakage in mouse colon tumors and human colon cancer cells.

  Molecular carcinogenesis 20120501

• Activation of the p53 pathway induces α-smooth muscle actin expression in both myeloid leukemic cells and normal macrophages.

  Journal of cellular physiology 20120501

• Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia.

  Leukemia 20120501

• p53 and MDM2 are involved in the regulation of osteocalcin gene expression.

  Experimental cell research 20120501

• An evaluation of small-molecule p53 activators as chemoprotectants ameliorating adverse effects of anticancer drugs in normal cells.

  Cell cycle (Georgetown, Tex.) 20120501

• Reversible induction of PARP1 degradation by p53-inducible cis-imidazoline compounds.

  Biochemical and biophysical research communications 20120427

• The MDM2 inhibitor Nutlin-3 modulates dendritic cell-induced T cell proliferation.

  Human immunology 20120401

• Nutlin-3 induces apoptosis, disrupts viral latency and inhibits expression of angiopoietin-2 in Kaposi sarcoma tumor cells.

  Cell cycle (Georgetown, Tex.) 20120401

• Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents.

  Cell death & disease 20120401

• Structural insights into the dual-targeting mechanism of Nutlin-3.

  Biochemical and biophysical research communications 20120330

• MDM2 antagonism by nutlin-3 induces death in human medulloblastoma cells.

  Neuroscience letters 20120328

• Synergistic growth inhibition based on small-molecule p53 activation as treatment for intraocular melanoma.

  Oncogene 20120301

• Decreased sensitivity of 17p-deleted chronic lymphocytic leukemia cells to a small molecule BCL-2 antagonist ABT-737.

  Cancer 20120215

• MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63.

  Oncogene 20120209

• Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression.

  Investigational new drugs 20120201

• p53 rescue through HDM2 antagonism suppresses melanoma growth and potentiates MEK inhibition.

  The Journal of investigative dermatology 20120201

• Inability of p53-reactivating compounds Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient in p53Ser46 phosphorylation.

  Biochemical and biophysical research communications 20120120

• Fibroid explants reveal a higher sensitivity against MDM2-inhibitor nutlin-3 than matching myometrium.

  BMC women's health 20120101

• Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

  PloS one 20120101

• p53 modulation as a therapeutic strategy in gastrointestinal stromal tumors.

  PloS one 20120101

• Binding of Translationally Controlled Tumour Protein to the N-terminal domain of HDM2 is inhibited by nutlin-3.

  PloS one 20120101

• HDM2 antagonist MI-219 (spiro-oxindole), but not Nutlin-3 (cis-imidazoline), regulates p53 through enhanced HDM2 autoubiquitination and degradation in human malignant B-cell lymphomas.

  Journal of hematology & oncology 20120101

• MEK-ERK signaling dictates DNA-repair gene MGMT expression and temozolomide resistance of stem-like glioblastoma cells via the MDM2-p53 axis.

  Stem cells (Dayton, Ohio) 20111201

• Synchronized release of Doxil and Nutlin-3 by remote degradation of polysaccharide matrices and its possible use in the local treatment of colorectal cancer.

  Journal of drug targeting 20111201

• Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells.

  Cell death & disease 20111201

• Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3.

  Oncogene 20111117

• MDM2-p53 protein-protein interaction inhibitors: a-ring substituted isoindolinones.

  Bioorganic & medicinal chemistry letters 20111001

• Inhibition of MDM2 attenuates neointimal hyperplasia via suppression of vascular proliferation and inflammation.

  Cardiovascular research 20110901

• Nutlin-3 downregulates the expression of the oncogene TCL1 in primary B chronic lymphocytic leukemic cells.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20110901

• The power of chemotherapeutic engineering: arresting cell cycle and suppressing senescence to protect from mitotic inhibitors.

  Cell cycle (Georgetown, Tex.) 20110715

• MDM2 antagonist nutlin-3a reverses mitoxantrone resistance by inhibiting breast cancer resistance protein mediated drug transport.

  Biochemical pharmacology 20110701

• A small-molecule p53 activator induces apoptosis through inhibiting MDMX expression in breast cancer cells.

  Neoplasia (New York, N.Y.) 20110701

• Treatment with a BH3 mimetic overcomes the resistance of latency III EBV (+) cells to p53-mediated apoptosis.

  Cell death & disease 20110701

• Targeting the p53 pathway in retinoblastoma with subconjunctival Nutlin-3a.

  Cancer research 20110615

• Anticancer effects of the p53 activator nutlin-3 in Ewing's sarcoma cells.

  European journal of cancer (Oxford, England : 1990) 20110601

• Functional analysis of the p53 pathway in neuroblastoma cells using the small-molecule MDM2 antagonist nutlin-3.

  Molecular cancer therapeutics 20110601

• Mechanism-specific signatures for small-molecule p53 activators.

  Cell cycle (Georgetown, Tex.) 20110515

• Understanding small-molecule binding to MDM2: insights into structural effects of isoindolinone inhibitors from NMR spectroscopy.

  Chemical biology & drug design 20110501

• Inhibition of Mdm2 sensitizes human retinal pigment epithelial cells to apoptosis.

  Investigative ophthalmology & visual science 20110501

• miR-34a induces the downregulation of both E2F1 and B-Myb oncogenes in leukemic cells.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20110501

• Activation of the p53 pathway by the MDM2 inhibitor nutlin-3a overcomes BCL2 overexpression in a preclinical model of diffuse large B-cell lymphoma associated with t(14;18)(q32;q21).

  Leukemia 20110501

• Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with Nutlin to induce p53-mediated apoptosis in solid tumors.

  Cell death & disease 20110501

• Synthetic protocol published for promising anticancer compound.

  Future medicinal chemistry 20110501

• An Mdm2 antagonist, Nutlin-3a, induces p53-dependent and proteasome-mediated poly(ADP-ribose) polymerase1 degradation in mouse fibroblasts.

  Biochemical and biophysical research communications 20110415

• Disruption of the MDM2-p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway.

  Cell death & disease 20110401

• Targeted nutlin-3a loaded nanoparticles inhibiting p53-MDM2 interaction: novel strategy for breast cancer therapy.

  Nanomedicine (London, England) 20110401

• Isoindolinone inhibitors of the murine double minute 2 (MDM2)-p53 protein-protein interaction: structure-activity studies leading to improved potency.

  Journal of medicinal chemistry 20110310

• Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells.

  Blood 20110303

• Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells.

  Cancer science 20110301

• Exploring long-term protection of normal human fibroblasts and epithelial cells from chemotherapy in cell culture.

  Oncotarget 20110301

• HMGA2 and p14Arf: major roles in cellular senescence of fibroids and therapeutic implications.

  Anticancer research 20110301

• Suppression of p53 activity through the cooperative action of Ski and histone deacetylase SIRT1.

  The Journal of biological chemistry 20110225

• Dasatinib plus Nutlin-3 shows synergistic antileukemic activity in both p53 wild-type and p53 mutated B chronic lymphocytic leukemias by inhibiting the Akt pathway.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20110215

• Molecular mimicry-based repositioning of nutlin-3 to anti-apoptotic Bcl-2 family proteins.

  Journal of the American Chemical Society 20110209

• Nutlin-3a is a potential therapeutic for ewing sarcoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20110201

• MDM2 antagonist can inhibit tumor growth in hepatocellular carcinoma with different types of p53 in vitro.

  Journal of gastroenterology and hepatology 20110201

• Epithelial cell adhesion molecule targeted nutlin-3a loaded immunonanoparticles for cancer therapy.

  Acta biomaterialia 20110101

• Mdm2 inhibition induces apoptosis in p53 deficient human colon cancer cells by activating p73- and E2F1-mediated expression of PUMA and Siva-1.

  Apoptosis : an international journal on programmed cell death 20110101

• p53-Reactivating small molecules induce apoptosis and enhance chemotherapeutic cytotoxicity in head and neck squamous cell carcinoma.

  Oral oncology 20110101

• Treatment of ovarian cancer cells with nutlin-3 and resveratrol combination leads to apoptosis via caspase activation.

  Journal of medicinal food 20110101

• A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation.

  BMC cancer 20110101

• Pharmacologic activation of p53 by small-molecule MDM2 antagonists.

  Current pharmaceutical design 20110101

• Recent advances in the therapeutic perspectives of Nutlin-3.

  Current pharmaceutical design 20110101

• Activation of p53 by nutlin-3a induces apoptosis and cellular senescence in human glioblastoma multiforme.

  PloS one 20110101

• MDM2 antagonists boost antitumor effect of androgen withdrawal: implications for therapy of prostate cancer.

  Molecular cancer 20110101

• MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines.

  BMC cancer 20110101

• Transcriptional and post-transcriptional mechanisms for oncogenic overexpression of ether à go-go K+ channel.

  PloS one 20110101

• Oncogenic functions of hMDMX in in vitro transformation of primary human fibroblasts and embryonic retinoblasts.

  Molecular cancer 20110101

• Elimination of proliferating cells unmasks the shift from senescence to quiescence caused by rapamycin.

  PloS one 20110101

• MDM2 antagonist Nutlin-3 enhances bortezomib-mediated mitochondrial apoptosis in TP53-mutated mantle cell lymphoma.

  Cancer letters 20101228

• p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation.

  Pigment cell & melanoma research 20101201

• mTOR and its link to the picture of Dorian Gray - re-activation of mTOR promotes aging.

  Aging 20101201

• Contrasting effects of nutlin-3 on TRAIL- and docetaxel-induced apoptosis due to upregulation of TRAIL-R2 and Mcl-1 in human melanoma cells.

  Molecular cancer therapeutics 20101201

• DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence.

  Aging 20101201

• Hypoxia downregulates p53 but induces apoptosis and enhances expression of BAD in cultures of human syncytiotrophoblasts.

  American journal of physiology. Cell physiology 20101101

• Shifting senescence into quiescence by turning up p53.

  Cell cycle (Georgetown, Tex.) 20101101

• Weak p53 permits senescence during cell cycle arrest.

  Cell cycle (Georgetown, Tex.) 20101101

• p53: The pivot between cell cycle arrest and senescence.

  Cell cycle (Georgetown, Tex.) 20101101

• The p53 inducing drug dosage may determine quiescence or senescence.

  Aging 20101101

• Evaluation of an Actinomycin D/VX-680 aurora kinase inhibitor combination in p53-based cyclotherapy.

  Oncotarget 20101101

• p53-dependent repression of polo-like kinase-1 (PLK1).

  Cell cycle (Georgetown, Tex.) 20101015

• Nutlin-3 cooperates with doxorubicin to induce apoptosis of human hepatocellular carcinoma cells through p53 or p73 signaling pathways.

  Journal of cancer research and clinical oncology 20101001

• HDMX-L is expressed from a functional p53-responsive promoter in the first intron of the HDMX gene and participates in an autoregulatory feedback loop to control p53 activity.

  The Journal of biological chemistry 20100917

• Molecular mechanisms of nutlin-induced apoptosis in multiple myeloma: evidence for p53-transcription-dependent and -independent pathways.

  Cancer biology & therapy 20100915

• Combination of nutlin-3 and VX-680 selectively targets p53 mutant cells with reversible effects on cells expressing wild-type p53.

  Cell death and differentiation 20100901

• Disruption of p73-MDM2 binding synergizes with gemcitabine to induce apoptosis in HuCCT1 cholangiocarcinoma cell line with p53 mutation.

  Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20100801

• The C terminus of p53 binds the N-terminal domain of MDM2.

  Nature structural & molecular biology 20100801

• Characterization and optimization of a novel protein-protein interaction biosensor high-content screening assay to identify disruptors of the interactions between p53 and hDM2.

  Assay and drug development technologies 20100801

• Nutlin-3, the small-molecule inhibitor of MDM2, promotes senescence and radiosensitises laryngeal carcinoma cells harbouring wild-type p53.

  British journal of cancer 20100713

• MDM4 (MDMX) is overexpressed in chronic lymphocytic leukaemia (CLL) and marks a subset of p53wild-type CLL with a poor cytotoxic response to Nutlin-3.

  British journal of haematology 20100701

• Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers.

  Cancer science 20100601

• Decision-making by p53 and mTOR.

  Aging 20100601

• The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway.

  Aging 20100601

• Enhancement of imatinib-induced apoptosis of BCR/ABL-expressing cells by nutlin-3 through synergistic activation of the mitochondrial apoptotic pathway.

  Apoptosis : an international journal on programmed cell death 20100501

• 1,25-dihydroxyvitamin D3 enhances the apoptotic activity of MDM2 antagonist nutlin-3a in acute myeloid leukemia cells expressing wild-type p53.

  Molecular cancer therapeutics 20100501

• Role of Mdm4 in drug sensitivity of breast cancer cells.

  Oncogene 20100422

• Therapeutic potential of Mdm2 inhibition in malignant germ cell tumours.

  European urology 20100401

• Inactivation of p53 signaling by p73 or PTEN ablation results in a transformed phenotype that remains susceptible to Nutlin-3 mediated apoptosis.

  Cell cycle (Georgetown, Tex.) 20100401

• Motexafin gadolinium enhances p53-Mdm2 interactions, reducing p53 and downstream targets in lymphoma cell lines.

  Anticancer research 20100401

• The oncogene DEK promotes leukemic cell survival and is downregulated by both Nutlin-3 and chlorambucil in B-chronic lymphocytic leukemic cells.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20100315

• Foxp3 expression in p53-dependent DNA damage responses.

  The Journal of biological chemistry 20100312

• Determination of nutlin-3a in murine plasma by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).

  Journal of pharmaceutical and biomedical analysis 20100311

• Phosphorylation of serine 392 in p53 is a common and integral event during p53 induction by diverse stimuli.

  Cellular signalling 20100301

• Perifosine plus nutlin-3 combination shows a synergistic anti-leukaemic activity.

  British journal of haematology 20100301

• Differential sensitivity of the inner ear sensory cell populations to forced cell cycle re-entry and p53 induction.

  Journal of neurochemistry 20100301

• DNA damage response to the Mdm2 inhibitor nutlin-3.

  Biochemical pharmacology 20100215

• The expression levels of the pro-apoptotic XAF-1 gene modulate the cytotoxic response to Nutlin-3 in B chronic lymphocytic leukemia.

  Leukemia 20100201

• Nutlin-3 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulation of death receptor 5 (DR5) in human sarcoma HOS cells and human colon cancer HCT116 cells.

  Cancer letters 20100101

• Selective FLT3 inhibitor FI-700 neutralizes Mcl-1 and enhances p53-mediated apoptosis in AML cells with activating mutations of FLT3 through Mcl-1/Noxa axis.

  Leukemia 20100101

• Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment.

  BMC cancer 20100101

• Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6.

  BMC cancer 20100101

• High level MycN expression in non-MYCN amplified neuroblastoma is induced by the combination treatment nutlin-3 and doxorubicin and enhances chemosensitivity.

  Oncology reports 20091201

• Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20091201

• Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction.

  Journal of medicinal chemistry 20091126

• Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53.

  Journal of the National Cancer Institute 20091118

• Differential microRNA-34a expression and tumor suppressor function in retinoblastoma cells.

  Investigative ophthalmology & visual science 20091001

• Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1alpha.

  Carcinogenesis 20091001

• Awakening p53 in senescent cells using nutlin-3.

  Aging 20091001

• Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3.

  Aging 20091001

• Nutlin-3 affects expression and function of retinoblastoma protein: role of retinoblastoma protein in cellular response to nutlin-3.

  The Journal of biological chemistry 20090925

• Activation of p53 by MDM2 antagonists has differential apoptotic effects on Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt's lymphoma cells.

  Leukemia 20090901

• Specific activation of the p53 pathway by low dose actinomycin D: a new route to p53 based cyclotherapy.

  Cell cycle (Georgetown, Tex.) 20090901

• MI-63: a novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53.

  British journal of cancer 20090901

• Correcting miR-15a/16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity.

  Molecular cancer therapeutics 20090901

• HIPK2 regulation by MDM2 determines tumor cell response to the p53-reactivating drugs nutlin-3 and RITA.

  Cancer research 20090801

• Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking.

  Bioorganic & medicinal chemistry letters 20090715

• Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20090615

• Exposure of B cell chronic lymphocytic leukemia (B-CLL) cells to nutlin-3 induces a characteristic gene expression profile, which correlates with nutlin-3-mediated cytotoxicity.

  Current cancer drug targets 20090601

• The MDM2 antagonist nutlin-3 sensitizes p53-null neuroblastoma cells to doxorubicin via E2F1 and TAp73.

  International journal of oncology 20090501

• Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism.

  Blood 20090430

• Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphoma.

  Leukemia 20090401

• Depletion of guanine nucleotides leads to the Mdm2-dependent proteasomal degradation of nucleostemin.

  Cancer research 20090401

• Reactivation of p53 function in synovial sarcoma cells by inhibition of p53-HDM2 interaction.

  Cancer letters 20090318

• Parthenolide promotes the ubiquitination of MDM2 and activates p53 cellular functions.

  Molecular cancer therapeutics 20090301

• MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20090201

• Reversal of P-glycoprotein-mediated multidrug resistance by the murine double minute 2 antagonist nutlin-3.

  Cancer research 20090115

• Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy.

  Annual review of pharmacology and toxicology 20090101

• Syntaxin 6, a regulator of the protein trafficking machinery and a target of the p53 family, is required for cell adhesion and survival.

  The Journal of biological chemistry 20081107

• Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance.

  Leukemia 20081101

• MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation.

  American journal of physiology. Renal physiology 20081101

• RHAMM is differentially expressed in the cell cycle and downregulated by the tumor suppressor p53.

  Cell cycle (Georgetown, Tex.) 20081101

• Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia.

  Blood 20081001

• E2F-1 transcriptional activity is a critical determinant of Mdm2 antagonist-induced apoptosis in human tumor cell lines.

  Oncogene 20080911

• The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML.

  Leukemia 20080901

• NMR screening for lead compounds using tryptophan-mutated proteins.

  Journal of medicinal chemistry 20080828

• Multiple p53-independent gene silencing mechanisms define the cellular response to p53 activation.

  Cell cycle (Georgetown, Tex.) 20080801

• A novel functional assay using etoposide plus nutlin-3a detects and distinguishes between ATM and TP53 mutations in CLL.

  Leukemia 20080701

• BH3 activation blocks Hdmx suppression of apoptosis and cooperates with Nutlin to induce cell death.

  Cell cycle (Georgetown, Tex.) 20080701

• Hdm2 and nitric oxide radicals contribute to the p53-dependent radioadaptive response.

  International journal of radiation oncology, biology, physics 20080601

• Quantitative lid dynamics of MDM2 reveals differential ligand binding modes of the p53-binding cleft.

  Journal of the American Chemical Society 20080521

• Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells.

  Journal of cellular biochemistry 20080515

• Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence.

  Cancer research 20080501

• Inhibition of the Akt/survivin pathway synergizes the antileukemia effect of nutlin-3 in acute lymphoblastic leukemia cells.

  Molecular cancer therapeutics 20080501

• Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5.

  Blood 20080401

• MDM2 antagonist nutlin-3 is a potent inducer of apoptosis in pediatric acute lymphoblastic leukemia cells with wild-type p53 and overexpression of MDM2.

  Leukemia 20080401

• Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53.

  Molecular cancer therapeutics 20080401

• HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function.

  Oncogene 20080207

• Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells.

  Journal of leukocyte biology 20080201

• Activation of the p53 pathway down-regulates the osteoprotegerin expression and release by vascular endothelial cells.

  Blood 20080201

• Disruption of the p53-Mdm2 complex by Nutlin-3 reveals different cancer cell phenotypes.

  Ethnicity & disease 20080101

• Exploration of liquid and supercritical fluid chromatographic chiral separation and purification of Nutlin-3--a small molecule antagonist of MDM2.

  Journal of pharmaceutical and biomedical analysis 20071221

• p53-mediated growth suppression in response to Nutlin-3 in cyclin D1 transformed cells occurs independently of p21.

  Cancer research 20071015

• MDM2 antagonist Nutlin-3 suppresses the proliferation and differentiation of human pre-osteoclasts through a p53-dependent pathway.

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20071001

• The MDM-2 antagonist nutlin-3 promotes the maturation of acute myeloid leukemic blasts.

  Neoplasia (New York, N.Y.) 20071001

• Respiratory syncytial virus decreases p53 protein to prolong survival of airway epithelial cells.

  Journal of immunology (Baltimore, Md. : 1950) 20070901

• Nutlin-3 inhibits the NFkappaB pathway in a p53-dependent manner: implications in lung cancer therapy.

  Cell cycle (Georgetown, Tex.) 20070901

• Hyperubiquitylation of wild-type p53 contributes to cytoplasmic sequestration in neuroblastoma.

  Cell death and differentiation 20070701

• Analysis of the MDM2 antagonist nutlin-3 in human prostate cancer cells.

  The Prostate 20070601

• Inhibition of p53-murine double minute 2 interaction by nutlin-3A stabilizes p53 and induces cell cycle arrest and apoptosis in Hodgkin lymphoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20070601

• Synergistic cytotoxic activity of recombinant TRAIL plus the non-genotoxic activator of the p53 pathway nutlin-3 in acute myeloid leukemia cells.

  Current drug metabolism 20070501

• Pharmacologic activation of p53-dependent and p53-independent apoptotic pathways in Hodgkin/Reed-Sternberg cells.

  Leukemia 20070401

• Mitogen-activated protein kinase kinase inhibition enhances nuclear proapoptotic function of p53 in acute myelogenous leukemia cells.

  Cancer research 20070401

• [TP53 and RB tumor suppressor pathways collaborate in retinoblastoma genesis].

  Medecine sciences : M/S 20070401

• Nutlin-3 protects kidney cells during cisplatin therapy by suppressing Bax/Bak activation.

  The Journal of biological chemistry 20070126

• Antiangiogenic activity of the MDM2 antagonist nutlin-3.

  Circulation research 20070105

• Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo.

  Cancer cell 20061201

• Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce mitochondrial apoptosis in AML.

  Cell cycle (Georgetown, Tex.) 20061201

• Hdmx modulates the outcome of p53 activation in human tumor cells.

  The Journal of biological chemistry 20061103

• Cancer biology: second step to retinal tumours.

  Nature 20061102

• Inactivation of the p53 pathway in retinoblastoma.

  Nature 20061102

• Nongenotoxic p53 activation protects cells against S-phase-specific chemotherapy.

  Cancer research 20061101

• Circumvention and reactivation of the p53 oncogene checkpoint in mouse colon tumors.

  Biochemical pharmacology 20061016

• Small-molecule MDM2 antagonists as a new therapy concept for neuroblastoma.

  Cancer research 20061001

• Small molecule inhibition of HDM2 leads to p53-mediated cell death in retinoblastoma cells.

  Archives of ophthalmology (Chicago, Ill. : 1960) 20060901

• MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell death.

  Molecular cancer therapeutics 20060901

• Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia.

  Blood 20060801

• A second p53 binding site in the central domain of Mdm2 is essential for p53 ubiquitination.

  Biochemistry 20060801

• (R)-roscovitine (CYC202, Seliciclib) sensitizes SH-SY5Y neuroblastoma cells to nutlin-3-induced apoptosis.

  Experimental cell research 20060715

• Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening strategy.

  Journal of medicinal chemistry 20060629

• The epithelial cell transforming sequence 2, a guanine nucleotide exchange factor for Rho GTPases, is repressed by p53 via protein methyltransferases and is required for G1-S transition.

  Cancer research 20060615

• Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL).

  Blood 20060515

• MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells.

  Blood 20060515

• An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors.

  Nature chemical biology 20060401

• Levels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3.

  Cancer research 20060315

• WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53.

  The Journal of biological chemistry 20051230

• Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma.

  Blood 20051115

• MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy.

  Blood 20051101

• Monitoring the effects of antagonists on protein-protein interactions with NMR spectroscopy.

  Journal of the American Chemical Society 20050928

• Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis.

  The Journal of biological chemistry 20041217