Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer

MIRROS: a randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia

(2020) Pau Montesinos et al.   Future Oncology

MDM2 promotes genome instability by ubiquitinating the transcription factor HBP1

(2019) Zhengyi Cao et al.   ONCOGENE

2OA phase Ib/II study of APG-115 in combination with pembrolizumab in patients with unresectable or metastatic melanomas or advanced solid tumors

(2019) A W Tolcher et al.   ANNALS OF ONCOLOGY

The past, present and future of potential small-molecule drugs targeting p53-MDM2/MDMX for cancer therapy

(2019) Yao Liu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors

(2019) Albiruni R. Abdul Razak et al.   INVESTIGATIONAL NEW DRUGS

MDM2 inhibitor APG-115 synergizes with PD-1 blockade through enhancing antitumor immunity in the tumor microenvironment

(2019) Douglas D. Fang et al.   Journal for ImmunoTherapy of Cancer

An Update on MDMX and Dual MDM2/X Inhibitors

(2018) Margarida Espadinha et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

MDM2- and FLT3-inhibitors in the treatment of FLT3-ITD acute myeloid leukemia, specificity and efficacy of NVP-HDM201 and midostaurin

(2018) Katja Seipel et al.   HAEMATOLOGICA

Simultaneous Targeting of RGD-Integrins and Dual Murine Double Minute Proteins in Glioblastoma Multiforme

(2018) Francesco Merlino et al.   JOURNAL OF MEDICINAL CHEMISTRY

MDM2- and FLT3-inhibitors in the treatment of FLT3-ITD acute myeloid leukemia, specificity and efficacy of NVP-HDM201 and midostaurin

(2018) Katja Seipel et al.   HAEMATOLOGICA

Dose and schedule determine distinct molecular mechanisms underlying the efficacy of the p53-MDM2 inhibitor HDM201

(2018) Sébastien Jeay et al.   CANCER RESEARCH

Small Molecules Simultaneously Inhibiting p53-Murine Double Minute 2 (MDM2) Interaction and Histone Deacetylases (HDACs): Discovery of Novel Multitargeting Antitumor Agents

(2018) Shipeng He et al.   JOURNAL OF MEDICINAL CHEMISTRY

A phase I study of the HDM2 antagonist SAR405838 combined with the MEK inhibitor pimasertib in patients with advanced solid tumours

(2018) Vincent A. de Weger et al.   BRITISH JOURNAL OF CANCER

Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma

(2018) Lindi Chen et al.   INTERNATIONAL JOURNAL OF CANCER

Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells

(2018) Lukasz Skalniak et al.   Cancers

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

Computer-Aided Identification and Lead Optimization of Dual Murine Double Minute 2 and 4 Binders: Structure–Activity Relationship Studies and Pharmacological Activity

(2017) Mariateresa Giustiniano et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 4-((3′R,4′S,5′R)-6″-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2″-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development

(2017) Angelo Aguilar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Dual Inhibitors of MDM2 and XIAP for Cancer Treatment

(2016) Lubing Gu et al.   CANCER CELL

Dual inhibition of nuclear factor kappa-B and Mdm2 enhance the antitumor effect of radiation therapy for pancreatic cancer

(2016) Yoshihiro Shirai et al.   CANCER LETTERS

Peptides and peptidomimetics in the p53/MDM2/MDM4 circuitry - a patent review

(2016) Emanuela Teveroni et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

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

Lead Optimization of 2-Phenylindolylglyoxylyldipeptide Murine Double Minute (MDM)2/Translocator Protein (TSPO) Dual Inhibitors for the Treatment of Gliomas

(2016) Simona Daniele et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: Cell cycle and proliferation-dependent regulation

(2016) Emil Mladenov et al.   SEMINARS IN CANCER BIOLOGY

Mdm2 as a chromatin modifier

(2016) Magdalena Wienken et al.   Journal of Molecular Cell Biology

Role of Mdm2 and Mdmx in DNA repair

(2016) Christine M. Eischen   Journal of Molecular Cell Biology

p53 in the DNA-Damage-Repair Process

(2016) Ashley B. Williams et al.   Cold Spring Harbor Perspectives in Medicine

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

(2016) Angel R. de Lera et al.   Clinical Epigenetics

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

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

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

SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma

(2015) K. L. J. Bill et al.   CLINICAL CANCER RESEARCH

Preclinical Efficacy of the MDM2 Inhibitor RG7112 in MDM2-Amplified and TP53 Wild-type Glioblastomas

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

Inhibition of MDM2 homodimerization by XIAP IRES stabilizes MDM2, influencing cancer cell survival

(2015) Tao Liu et al.   Molecular Cancer

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

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

(2014) S. Wang et al.   CANCER RESEARCH

The Mdm Network and Its Regulation of p53 Activities: A Rheostat of Cancer Risk

(2014) Christine M. Eischen et al.   HUMAN MUTATION

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

Double-Edged Swords as Cancer Therapeutics: Novel, Orally Active, Small Molecules Simultaneously Inhibit p53–MDM2 Interaction and the NF-κB Pathway

(2014) Chunlin Zhuang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Causes of Genome Instability

(2013) Andrés Aguilera et al.   Annual Review of Genetics

The translocator protein (TSPO): A novel target for cancer chemotherapy

(2013) Christopher J.D. Austin et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Auto-ubiquitination of Mdm2 Enhances Its Substrate Ubiquitin Ligase Activity

(2013) Ruchira S. Ranaweera et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The human oncoprotein MDM2 induces replication stress eliciting early intra-S-phase checkpoint response and inhibition of DNA replication origin firing

(2013) R. A. Frum et al.   NUCLEIC ACIDS RESEARCH

MDM2’s social network

(2013) R Fåhraeus et al.   ONCOGENE

Endogenous Human MDM2-C Is Highly Expressed in Human Cancers and Functions as a p53-Independent Growth Activator

(2013) Danielle R. Okoro et al.   PLoS One

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

(2013) Binh Vu et al.   ACS Medicinal Chemistry Letters

Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation

(2011) Carlos Mas-Moruno et al.   Anti-Cancer Agents in Medicinal Chemistry

Inhibition of p53 DNA Binding Function by the MDM2 Protein Acidic Domain

(2011) Brittany Cross et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

(2011) E McCormack et al.   LEUKEMIA

Regulation of MDM2 E3 Ligase Activity by Phosphorylation after DNA Damage

(2011) Q. Cheng et al.   MOLECULAR AND CELLULAR BIOLOGY

Stabilization of Suv39H1 by SirT1 Is Part of Oxidative Stress Response and Ensures Genome Protection

(2011) Laia Bosch-Presegué et al.   MOLECULAR CELL

Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression

(2011) T Lushnikova et al.   ONCOGENE

Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development

(2010) Flavia Pichiorri et al.   CANCER CELL

Privileged scaffolds for library design and drug discovery

(2010) Matthew E Welsch et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents

(2010) Jiahuai Tan et al.   Journal of Hematology & Oncology

The DNA Damage Response: Making It Safe to Play with Knives

(2010) Alberto Ciccia et al.   MOLECULAR CELL

Mitochondria and cell death: outer membrane permeabilization and beyond

(2010) Stephen W. G. Tait et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Mdm2 Affects Genome Stability Independent of p53

(2009) A. Bouska et al.   CANCER RESEARCH

Modes of p53 Regulation

(2009) Jan-Philipp Kruse et al.   CELL

ATM activates p53 by regulating MDM2 oligomerization and E3 processivity

(2009) Qian Cheng et al.   EMBO JOURNAL

MDM2 and MDM4 splicing: an integral part of the cancer spliceome

(2009) Selvi Jeyaraj   Frontiers in Bioscience-Landmark

The MDM2-A Splice Variant of MDM2 Alters Transformation In vitro and the Tumor Spectrum in Both Arf- and p53-Null Models of Tumorigenesis

(2009) E. L. Volk et al.   MOLECULAR CANCER RESEARCH

The DNA-damage response in human biology and disease

(2009) Stephen P. Jackson et al.   NATURE

p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug

(2009) Shu-Ping Wang et al.   NATURE CELL BIOLOGY

DNA Damage, Aging, and Cancer

(2009) Jan H.J. Hoeijmakers   NEW ENGLAND JOURNAL OF MEDICINE

The regulation of MDM2 by multisite phosphorylation—Opportunities for molecular-based intervention to target tumours?

(2009) David W. Meek et al.   SEMINARS IN CANCER BIOLOGY

Acetylation Is Indispensable for p53 Activation

(2008) Yi Tang et al.   CELL

MDM2 SNP309 Is Associated With Poor Outcome in B-Cell Chronic Lymphocytic Leukemia

(2008) Irina Gryshchenko et al.   JOURNAL OF CLINICAL ONCOLOGY

Mdm2 Promotes Genetic Instability and Transformation Independent of p53

(2008) A. Bouska et al.   MOLECULAR AND CELLULAR BIOLOGY

ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation

(2008) Jer-Yen Yang et al.   NATURE CELL BIOLOGY

p53 mRNA controls p53 activity by managing Mdm2 functions

(2008) Marco M. Candeias et al.   NATURE CELL BIOLOGY

The genetics of the p53 pathway, apoptosis and cancer therapy

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

Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-κB pathways

(2008) Anwesha Dey et al.   NATURE REVIEWS DRUG DISCOVERY

Activation of the Cellular DNA Damage Response in the Absence of DNA Lesions

(2008) E. Soutoglou et al.   SCIENCE

SUMO-Specific Protease 2 Is Essential for Modulating p53-Mdm2 in Development of Trophoblast Stem Cell Niches and Lineages

(2008) Shang-Yi Chiu et al.   PLOS BIOLOGY