MDM2/X inhibitors under clinical evaluation: perspectives for the management of hematological malignancies and pediatric cancer

A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours

(2017) Maja de Jonge et al.   EUROPEAN JOURNAL OF CANCER

Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors

(2017) Andrew J. Wagner et al.   JOURNAL OF CLINICAL ONCOLOGY

Additional–structural–chromosomal aberrations are associated with inferior clinical outcome in patients with hyperdiploid multiple myeloma: a single-institution experience

(2017) Adrian A Carballo-Zarate et al.   MODERN PATHOLOGY

Unbalancing p53/Mdm2/IGF-1R axis by Mdm2 activation restrains the IGF-1-dependent invasive phenotype of skin melanoma

(2017) C Worrall et al.   ONCOGENE

Discovery of a novel class of highly potent inhibitors of the p53–MDM2 interaction by structure-based design starting from a conformational argument

(2016) Pascal Furet et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia

(2016) F. Nadeu et al.   BLOOD

The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

(2016) Elizabeth C. Townsend et al.   CANCER CELL

The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

(2016) Elizabeth C. Townsend et al.   CANCER CELL

Abstract 1224: Insights into the mechanism of action of NVP-HDM201, a differentiated and versatile Next-Generation small-molecule inhibitor of Mdm2, under evaluation in phase I clinical trials

(2016) Stéphane Ferretti et al.   CANCER RESEARCH

Abstract 1239: NVP-HDM201: Biochemical and biophysical profile of a novel highly potent and selective PPI inhibitor of p53-Mdm2

(2016) Thérèse Stachyra-Valat et al.   CANCER RESEARCH

Abstract 4855: Discovery of NVP-HDM201 - First disclosure of a Next-Generation Mdm2 inhibitor with superior characteristics

(2016) Philipp Holzer et al.   CANCER RESEARCH

Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia

(2016) Ling-Wen Ding et al.   CANCER RESEARCH

Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer

(2016) Vikram B. Wali et al.   CANCER RESEARCH

A Review of Stapled Peptides and Small Molecules to Inhibit Protein–Protein Interactions in Cancer

(2016) Vidhya Iyer   CURRENT MEDICINAL CHEMISTRY

Dose- and regimen-finding phase I study of NVP-HDM201 in patients (pts) with TP53 wild-type (wt) advanced tumors

(2016) D. Hyman et al.   EUROPEAN JOURNAL OF CANCER

Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2-selective antagonist idasanutlin (RG7388)

(2016) Frank Herting et al.   EUROPEAN JOURNAL OF HAEMATOLOGY

Acute myeloid leukemia patients clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts

(2016) B. Reis et al.   HAEMATOLOGICA

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

(2016) Christian Lehmann et al.   Journal of Hematology & Oncology

Centrosome associated genes pattern for risk sub-stratification in multiple myeloma

(2016) Fedor Kryukov et al.   Journal of Translational Medicine

p53 pathway dysfunction is highly prevalent in acute myeloid leukemia independent of TP53 mutational status

(2016) A Quintás-Cardama et al.   LEUKEMIA

A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML)

(2016) Farhad Ravandi et al.   LEUKEMIA RESEARCH

New monoclonal antibodies for the treatment of acute lymphoblastic leukemia

(2016) Nosha Farhadfar et al.   LEUKEMIA RESEARCH

Medicinal Chemistry Strategies to Disrupt the p53-MDM2/MDMX Interaction

(2016) Agostinho Lemos et al.   MEDICINAL RESEARCH REVIEWS

Allosteric Interactions byp53mRNA Govern HDM2 E3 Ubiquitin Ligase Specificity under Different Conditions

(2016) Ixaura Medina-Medina et al.   MOLECULAR AND CELLULAR BIOLOGY

TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes

(2016) John S. Welch et al.   NEW ENGLAND JOURNAL OF MEDICINE

Genomic Classification and Prognosis in Acute Myeloid Leukemia

(2016) Elli Papaemmanuil et al.   NEW ENGLAND JOURNAL OF MEDICINE

TRIMming p53’s anticancer activity

(2016) S Elabd et al.   ONCOGENE

Initial Testing (Stage 1) of MK-8242-A Novel MDM2 Inhibitor-by the Pediatric Preclinical Testing Program

(2016) Min H. Kang et al.   PEDIATRIC BLOOD & CANCER

TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma

(2016) Joonil Jung et al.   Nature Communications

The Role of MDM2 Amplification and Overexpression in Tumorigenesis

(2016) Jonathan D. Oliner et al.   Cold Spring Harbor Perspectives in Medicine

Acute myeloid leukemia patients clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts

(2016) B. Reis et al.   HAEMATOLOGICA

The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose-intensive chemotherapy including rituximab

(2015) Maribel Forero-Castro et al.   BRITISH JOURNAL OF HAEMATOLOGY

Clinical pharmacology characterization of RG7112, an MDM2 antagonist, in patients with advanced solid tumors

(2015) Amita Patnaik et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

How To Design a Successful p53-MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures

(2015) Natalia Estrada-Ortiz et al.   ChemMedChem

Mechanisms of p53 degradation

(2015) Chuck C.-K. Chao   CLINICA CHIMICA ACTA

Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia

(2015) M. Andreeff et al.   CLINICAL CANCER RESEARCH

Effective Targeting of the P53-MDM2 Axis in Preclinical Models of Infant MLL-Rearranged Acute Lymphoblastic Leukemia

(2015) J. Richmond et al.   CLINICAL CANCER RESEARCH

Elucidation of Acquired Resistance to Bcl-2 and MDM2 Inhibitors in Acute Leukemia In Vitro and In Vivo

(2015) C. G. Hoffman-Luca et al.   CLINICAL CANCER RESEARCH

Analysis of MDM2 Amplification in 43 Endometrial Stromal Tumors

(2015) J. Kenneth Schoolmeester et al.   INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY

The MDM2 RING Domain and Central Acidic Domain Play Distinct Roles in MDM2 Protein Homodimerization and MDM2-MDMX Protein Heterodimerization

(2015) Patrick L. Leslie et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma

(2015) Brian A. Walker et al.   JOURNAL OF CLINICAL ONCOLOGY

Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors

(2015) Philipp Holzer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097

(2015) E. Weisberg et al.   MOLECULAR CANCER THERAPEUTICS

Small Molecule Inhibition of MDM2-p53 Interaction Augments Radiation Response in Human Tumors

(2015) L. R. Werner et al.   MOLECULAR CANCER THERAPEUTICS

Potentiation of Carboplatin-Mediated DNA Damage by the Mdm2 Modulator Nutlin-3a in a Humanized Orthotopic Breast-to-Lung Metastatic Model

(2015) E. Tonsing-Carter et al.   MOLECULAR CANCER THERAPEUTICS

The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents

(2015) J. Canon et al.   MOLECULAR CANCER THERAPEUTICS

MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by AMP Kinase Activation

(2015) Gautam Borthakur et al.   PLoS One

Significant Differences in the Development of Acquired Resistance to the MDM2 Inhibitor SAR405838 between In Vitro and In Vivo Drug Treatment

(2015) C. Gianna Hoffman-Luca et al.   PLoS One

Prognostic signature and clonality pattern of recurrently mutated genes in inactive chronic lymphocytic leukemia

(2015) A M Hurtado et al.   Blood Cancer Journal

The p53 transcriptional pathway is preserved in ATMmutated and NOTCH1mutated chronic lymphocytic leukemias

(2015) Emmanouil Athanasakis et al.   Oncotarget

Sodium dichloroacetate exhibits anti-leukemic activity in B-chronic lymphocytic leukemia (B-CLL) and synergizes with the p53 activator Nutlin-3

(2015) Chiara Agnoletto et al.   Oncotarget

The regulation of MDM2 oncogene and its impact on human cancers

(2014) Y. Zhao et al.   ACTA BIOCHIMICA ET BIOPHYSICA SINICA

MDM2 Copy Numbers in Well-Differentiated and Dedifferentiated Liposarcoma

(2014) Patrick L. Ware et al.   AMERICAN JOURNAL OF CLINICAL PATHOLOGY

Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial

(2014) S. Stilgenbauer et al.   BLOOD

Declining childhood and adolescent cancer mortality: Great progress but still much to be done

(2014) Kathy Pritchard-Jones et al.   CANCER

Declining childhood and adolescent cancer mortality

(2014) Malcolm A. Smith et al.   CANCER

Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy

(2014) Jens G. Lohr et al.   CANCER CELL

SAR405838: An Optimized Inhibitor of MDM2-p53 Interaction That Induces Complete and Durable Tumor Regression

(2014) S. Wang et al.   CANCER RESEARCH

Mdm2 and Aurora Kinase A Inhibitors Synergize to Block Melanoma Growth by Driving Apoptosis and Immune Clearance of Tumor Cells

(2014) A. E. Vilgelm et al.   CANCER RESEARCH

Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain

(2014) Grzegorz Popowicz et al.   CELL CYCLE

TP53mutations andMDM2SNP309identify subgroups of AML patients with impaired outcome

(2014) Ingrid Jakobsen Falk et al.   EUROPEAN JOURNAL OF HAEMATOLOGY

Limiting the power of p53 through the ubiquitin proteasome pathway

(2014) Vinod Pant et al.   GENES & DEVELOPMENT

Discovery of AMG 232, a Potent, Selective, and Orally Bioavailable MDM2–p53 Inhibitor in Clinical Development

(2014) Daqing Sun et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recurrent mutations refine prognosis in chronic lymphocytic leukemia

(2014) P Baliakas et al.   LEUKEMIA

Drug discovery in paediatric oncology: roadblocks to progress

(2014) Peter C. Adamson et al.   Nature Reviews Clinical Oncology

The Functional TP53 rs1042522 and MDM4 rs4245739 Genetic Variants Contribute to Non-Hodgkin Lymphoma Risk

(2014) Chuanbo Fan et al.   PLoS One

MDM4 Overexpressed in Acute Myeloid Leukemia Patients with Complex Karyotype and Wild-Type TP53

(2014) Li Li et al.   PLoS One

Heterogeneity of genomic evolution and mutational profiles in multiple myeloma

(2014) Niccolo Bolli et al.   Nature Communications

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

(2013) Z. Y. Xu-Monette et al.   BLOOD

The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis

(2013) Z. R. Hunter et al.   BLOOD

p53-Based cyclotherapy: exploiting the ‘guardian of the genome’ to protect normal cells from cytotoxic therapy

(2013) B Rao et al.   BRITISH JOURNAL OF CANCER

Pharmacologic activation of wild-type p53 by nutlin therapy in childhood cancer

(2013) Tom Van Maerken et al.   CANCER LETTERS

Nanoparticles Engineered with Rituximab and Loaded with Nutlin-3 Show Promising Therapeutic Activity in B-Leukemic Xenografts

(2013) R. Voltan et al.   CLINICAL CANCER RESEARCH

Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells

(2013) V Tisato et al.   Clinics

Nanoparticles Loaded with Nutlin-3 Display Cytotoxicity Towards p53wildtype JVM-2 But Not Towards p53mutated BJAB Leukemic Cells

(2013) R. Voltan et al.   CURRENT MEDICINAL CHEMISTRY

Childhood cancer survivorship

(2013) Saro H. Armenian et al.   CURRENT OPINION IN PEDIATRICS

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemia

(2013) F. Nguyen-Khac et al.   HAEMATOLOGICA

Detection of TP53 dysfunction in chronic lymphocytic leukemia by an in vitro functional assay based on TP53 activation by the non-genotoxic drug Nutlin-3: a proposal for clinical application

(2013) Federico Pozzo et al.   Journal of Hematology & Oncology

Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development

(2013) Qingjie Ding et al.   JOURNAL OF MEDICINAL CHEMISTRY

Blocking ETV6/RUNX1-induced MDM2 overexpression by Nutlin-3 reactivates p53 signaling in childhood leukemia

(2013) U Kaindl et al.   LEUKEMIA

Mutational landscape and significance across 12 major cancer types

(2013) Cyriac Kandoth et al.   NATURE

The mutant p53 mouse as a pre-clinical model

(2013) J G Jackson et al.   ONCOGENE

Stapled α−helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy

(2013) Yong S. Chang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies

(2012) Z. Y. Xu-Monette et al.   BLOOD

TP53 pathway analysis in paediatric Burkitt lymphoma reveals increased MDM4 expression as the only TP53 pathway abnormality detected in a subset of cases

(2012) Vasiliki Leventaki et al.   BRITISH JOURNAL OF HAEMATOLOGY

S-MDM4 mRNA overexpression indicates a poor prognosis and marks a potential therapeutic target in chronic lymphocytic leukemia

(2012) Ling Liu et al.   CANCER SCIENCE

High-Throughput Genomic Analysis in Waldenström's Macroglobulinemia

(2012) Stéphanie Poulain et al.   Clinical Lymphoma Myeloma & Leukemia

Mdm2 and MdmX partner to regulate p53

(2012) Xinjiang Wang et al.   FEBS LETTERS

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

(2012) G. Zauli et al.   HAEMATOLOGICA

Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study

(2012) Isabelle Ray-Coquard et al.   LANCET ONCOLOGY

Drug Resistance to Inhibitors of the Human Double Minute-2 E3 Ligase Is Mediated by Point Mutations of p53, but Can Be Overcome with the p53 Targeting Agent RITA

(2012) R. J. Jones et al.   MOLECULAR CANCER THERAPEUTICS

Selective induction of TP53I3/p53-inducible gene 3 (PIG3) in myeloid leukemic cells, but not in normal cells, by Nutlin-3

(2012) Rebecca Voltan et al.   MOLECULAR CARCINOGENESIS

p53 mutations in cancer

(2012) Patricia A. J. Muller et al.   NATURE CELL BIOLOGY

Initial testing of the MDM2 inhibitor RG7112 by the pediatric preclinical testing program

(2012) Hernan Carol et al.   PEDIATRIC BLOOD & CANCER

Effect of MDM2 and vascular endothelial growth factor inhibition on tumor angiogenesis and metastasis in neuroblastoma

(2011) Danielle M. Patterson et al.   ANGIOGENESIS

Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma

(2011) R. Kridel et al.   BLOOD

Nutlin-3 Downregulates the Expression of the Oncogene TCL1 in Primary B Chronic Lymphocytic Leukemic Cells

(2011) R. Voltan et al.   CLINICAL CANCER RESEARCH

miR-34a Induces the Downregulation of Both E2F1 and B-Myb Oncogenes in Leukemic Cells

(2011) G. Zauli et al.   CLINICAL CANCER RESEARCH

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

(2011) M H Aziz et al.   ONCOGENE

Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group

(2010) M. Salido et al.   BLOOD

Multiple distinct molecular mechanisms influence sensitivity and resistance to MDM2 inhibitors in adult acute myelogenous leukemia

(2010) J. Long et al.   BLOOD

Making sense of ubiquitin ligases that regulate p53

(2010) Abhinav K. Jain et al.   CANCER BIOLOGY & THERAPY

A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53

(2010) Federico Bernal et al.   CANCER CELL

Epidemiology of childhood cancer

(2010) Peter Kaatsch   CANCER TREATMENT REVIEWS

Dasatinib Plus Nutlin-3 Shows Synergistic Antileukemic Activity in Both p53wild-type and p53mutated B Chronic Lymphocytic Leukemias by Inhibiting the Akt Pathway

(2010) G. Zauli et al.   CLINICAL CANCER RESEARCH

The Oncogene DEK Promotes Leukemic Cell Survival and Is Downregulated by both Nutlin-3 and Chlorambucil in B-Chronic Lymphocytic Leukemic Cells

(2010) P. Secchiero et al.   CLINICAL CANCER RESEARCH

The p53 orchestra: Mdm2 and Mdmx set the tone

(2010) Mark Wade et al.   TRENDS IN CELL BIOLOGY

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

(2009) P. Secchiero et al.   BLOOD

Identification of Copy Number Abnormalities and Inactivating Mutations in Two Negative Regulators of Nuclear Factor- B Signaling Pathways in Waldenstrom's Macroglobulinemia

(2009) E. Braggio et al.   CANCER RESEARCH

Ubiquitin-independent p53 proteasomal degradation

(2009) P Tsvetkov et al.   CELL DEATH AND DIFFERENTIATION

Escape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14ARF-MDM2-p53 axis

(2009) T Van Maerken et al.   CELL DEATH AND DIFFERENTIATION

Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis

(2009) Eun-Woo Lee et al.   EMBO JOURNAL

Inhibitors of MDM2 and MDMX: a structural perspective

(2009) Christiane Riedinger et al.   Future Medicinal Chemistry

Frequency and prognostic significance of murine double minute protein-2 overexpression and p53 gene mutations in childhood acute lymphoblastic leukemia

(2009) Olfat M. Hendy et al.   Hematology

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

(2009) P Secchiero et al.   LEUKEMIA

Trim24 targets endogenous p53 for degradation

(2009) Kendra Allton et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study

(2008) K. H. Young et al.   BLOOD

The genetics of the p53 pathway, apoptosis and cancer therapy

(2008) Alexei Vazquez et al.   NATURE REVIEWS DRUG DISCOVERY