MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents

Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer

(2020) TAKAYUKI NAKANO et al.   ANTICANCER RESEARCH

Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML

(2020) Courtney D. DiNardo et al.   BLOOD

Saga of Mcl-1: regulation from transcription to degradation

(2020) Viacheslav V. Senichkin et al.   CELL DEATH AND DIFFERENTIATION

AMG-176, an Mcl-1 antagonist, shows preclinical efficacy in chronic lymphocytic leukemia

(2020) Xue Yi et al.   CLINICAL CANCER RESEARCH

Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma

(2020) Richa Bajpai et al.   Nature Communications

Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Acute Myeloid Leukemia Patients

(2020) Shanshan Pei et al.   Cancer Discovery

Efficacy of venetoclax in high risk relapsed mantle cell lymphoma ( MCL ) ‐ outcomes and mutation profile from venetoclax resistant MCL patients

(2020) Shuangtao Zhao et al.   AMERICAN JOURNAL OF HEMATOLOGY

Venetoclax plus LDAC for patients with untreated AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial

(2020) Andrew Henry Wei et al.   BLOOD

Trametinib potentiates TRAIL‐induced apoptosis via FBW7‐dependent Mcl‐1 degradation in colorectal cancer cells

(2020) Lin Lin et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes

(2020) Carolane Seiller et al.   Cell Death & Disease

MCL1 inhibition is effective against a subset of small-cell lung cancer with high MCL1 and low BCL-XL expression

(2020) Yuto Yasuda et al.   Cell Death & Disease

BCL-2 Proteins in Pathogenesis and Therapy of B-Cell Non-Hodgkin Lymphomas

(2020) Magdalena Klanova et al.   Cancers

Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy

(2020) Chong Chyn Chua et al.   JOURNAL OF CLINICAL ONCOLOGY

Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies

(2020) Yonghan He et al.   Journal of Hematology & Oncology

Ubiquitination and deubiquitination of MCL1 in cancer: deciphering chemoresistance mechanisms and providing potential therapeutic options

(2020) Xiaowei Wu et al.   Cell Death & Disease

Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins

(2019) Rumani Singh et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers

(2019) K. Louault et al.   ONCOGENE

Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells

(2019) Warren Fiskus et al.   Blood Cancer Journal

Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis

(2019) Mohamed Elgendy et al.   CANCER CELL

Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Mantle Cell Lymphoma

(2019) Dana Prukova et al.   CLINICAL CANCER RESEARCH

Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer

(2019) Taekyu Lee et al.   JOURNAL OF MEDICINAL CHEMISTRY

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1 (MCL1)

(2019) James William Papatzimas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Molecular Comprehension of Mcl-1: From Gene Structure to Cancer Therapy

(2019) Viacheslav V. Senichkin et al.   TRENDS IN CELL BIOLOGY

Increased MCL-1 expression predicts poor prognosis and disease recurrence in acute myeloid leukemia

(2019) Xi-xi Li et al.   OncoTargets and Therapy

BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival

(2019) Erinna F. Lee et al.   Cell Death & Disease

Discovery of β-carboline copper(II) complexes as Mcl-1 inhibitor and in vitro and in vivo activity in cancer models

(2019) Xing Lu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Phenotype-based drug screening reveals association between venetoclax response and differentiation stage in acute myeloid leukemia

(2019) Heikki Kuusanmäki et al.   HAEMATOLOGICA

Structure-Guided Discovery of a Selective Mcl-1 Inhibitor with Cellular Activity

(2019) Zoltan Szlávik et al.   JOURNAL OF MEDICINAL CHEMISTRY

Treatment of Relapsed/Refractory Non Hodgkin Lymphoma Patients with Venetoclax Therapy: A Single-Center Evaluation of off-label use

(2019) Mitchell E. Hughes et al.   Clinical Lymphoma Myeloma & Leukemia

Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands

(2019) Ziqian Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Phase 1, First-in-Human Study of AMG 176, a Selective MCL-1 Inhibitor, in Patients With Relapsed or Refractory Multiple Myeloma

(2019) Andrew Spencer et al.   Clinical Lymphoma Myeloma & Leukemia

Specific interactions of BCL-2 family proteins mediate sensitivity to BH3-mimetics in diffuse large B-cell lymphoma

(2019) Victoria M. Smith et al.   HAEMATOLOGICA

Hot-Spots of Mcl-1 Protein

(2019) Camille Denis et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting melanoma’s MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors

(2019) Matthew J. Sale et al.   Nature Communications

Side-by-side comparison of BH3-mimetics identifies MCL-1 as a key therapeutic target in AML

(2019) Larissa Ewald et al.   Cell Death & Disease

Diminished apoptotic priming and ATM signalling confer a survival advantage onto aged haematopoietic stem cells in response to DNA damage

(2018) Paula Gutierrez-Martinez et al.   NATURE CELL BIOLOGY

MCL-1 is a prognostic indicator and drug target in breast cancer

(2018) Kirsteen J. Campbell et al.   Cell Death & Disease

Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic inhibitors

(2018) Shengzhe Zhang et al.   Nature Communications

A Non-apoptotic Function of MCL-1 in Promoting Pluripotency and Modulating Mitochondrial Dynamics in Stem Cells

(2018) Megan L. Rasmussen et al.   Stem Cell Reports

Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia

(2018) Donia M. Moujalled et al.   LEUKEMIA

Gene essentiality landscape and druggable oncogenic dependencies in herpesviral primary effusion lymphoma

(2018) Mark Manzano et al.   Nature Communications

A Novel MCL-1 Inhibitor Combined with Venetoclax Rescues Venetoclax Resistant Acute Myelogenous Leukemia

(2018) Haley E. Ramsey et al.   Cancer Discovery

Exploiting MCL-1 dependency with combination MEK + MCL-1 inhibitors leads to induction of apoptosis and tumor regression in KRAS mutant non-small cell lung cancer

(2018) Varuna Nangia et al.   Cancer Discovery

BH3-mimetic toolkit guides the respective use of BCL2 and MCL1 BH3-mimetics in myeloma treatment

(2018) Patricia Gomez-Bougie et al.   BLOOD

Rationally derived drug combinations with the novel Mcl-1 inhibitor EU-5346 in breast cancer

(2018) Sonia Vallet et al.   BREAST CANCER RESEARCH AND TREATMENT

Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia

(2018) Adriana E. Tron et al.   Nature Communications

Role and Regulation of Pro-survival BCL-2 Proteins in Multiple Myeloma

(2018) Anne Slomp et al.   Frontiers in Oncology

Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling

(2017) Simon J. Cook et al.   FEBS Journal

Targeting Mcl-1 enhances DNA replication stress sensitivity to cancer therapy

(2017) Guo Chen et al.   JOURNAL OF CLINICAL INVESTIGATION

Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

(2017) Matthew S. Davids et al.   JOURNAL OF CLINICAL ONCOLOGY

Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

(2017) Delphine Merino et al.   Science Translational Medicine

Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy

(2017) Akane Inoue-Yamauchi et al.   Nature Communications

AACR Project GENIE: Powering Precision Medicine through an International Consortium

(2017)   Cancer Discovery

BCR signaling inhibitors differ in their ability to overcome Mcl-1-mediated resistance of CLL B cells to ABT-199

(2016) K. Bojarczuk et al.   BLOOD

Hierarchy for targeting prosurvival BCL2 family proteins in multiple myeloma: pivotal role of MCL1

(2016) J.-N. Gong et al.   BLOOD

Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise

(2016) Kristopher A. Sarosiek et al.   FEBS Journal

Re-activation of mitochondrial apoptosis inhibits T-cell lymphoma survival and treatment resistance

(2016) S Spinner et al.   LEUKEMIA

Key Survival Factor, Mcl-1, Correlates with Sensitivity to Combined Bcl-2/Bcl-xL Blockade

(2016) Michelle M. Williams et al.   MOLECULAR CANCER RESEARCH

Mutant BRAF Upregulates MCL-1 to Confer Apoptosis Resistance that Is Reversed by MCL-1 Antagonism and Cobimetinib in Colorectal Cancer

(2016) Hisato Kawakami et al.   MOLECULAR CANCER THERAPEUTICS

BCL2 Inhibitors as Anticancer Drugs: A Plethora of Misleading BH3 Mimetics

(2016) R. S. Soderquist et al.   MOLECULAR CANCER THERAPEUTICS

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

(2016) András Kotschy et al.   NATURE

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

(2016) J Tong et al.   ONCOGENE

Oncogenic mutations in the FBXW7 gene of adult T-cell leukemia patients

(2016) Chien-Hung Yeh et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Use of a MCL-1 inhibitor alone to de-bulk melanoma and in combination to kill melanoma initiating cells

(2016) Nabanita Mukherjee et al.   Oncotarget

BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells

(2016) Kan He et al.   Oncotarget

Targeting MCL-1/BCL-XL Forestalls the Acquisition of Resistance to ABT-199 in Acute Myeloid Leukemia

(2016) Kevin H. Lin et al.   Scientific Reports

Loss of a Single Mcl-1 Allele Inhibits MYC-Driven Lymphomagenesis by Sensitizing Pro-B Cells to Apoptosis

(2016) Stephanie Grabow et al.   Cell Reports

Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies

(2015) L. F. Peterson et al.   BLOOD

Inhibition of Mcl-1 with the pan-Bcl-2 family inhibitor (-)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia

(2015) R. Pan et al.   BLOOD

BH3 profiling identifies heterogeneous dependency on Bcl-2 family members in multiple myeloma and predicts sensitivity to BH3 mimetics

(2015) C Touzeau et al.   LEUKEMIA

Mutated Ptpn11 alters leukemic stem cell frequency and reduces the sensitivity of acute myeloid leukemia cells to Mcl1 inhibition

(2015) L Chen et al.   LEUKEMIA

Loss in MCL-1 function sensitizes non-Hodgkin’s lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199)

(2015) D C Phillips et al.   Blood Cancer Journal

Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells

(2015) Kim De Veirman et al.   Oncotarget

CDK9 inhibition by dinaciclib potently suppresses Mcl-1 to induce durable apoptotic responses in aggressive MYC-driven B-cell lymphoma in vivo

(2015) G P Gregory et al.   LEUKEMIA

Somatic mutations in myeloid cell leukemia-1 contribute to the pathogenesis of glioma by prolonging its half-life

(2015) XIUPENG LV et al.   Molecular Medicine Reports

Designed BH3 Peptides with High Affinity and Specificity for Targeting Mcl-1 in Cells

(2014) Glenna Wink Foight et al.   ACS Chemical Biology

MCL-1 but not BCL-XL is critical for the development and sustained expansion of thymic lymphoma in p53-deficient mice

(2014) S. Grabow et al.   BLOOD

Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53

(2014) G. L. Kelly et al.   GENES & DEVELOPMENT

Comprehensive molecular profiling of lung adenocarcinoma

(2014) Eric A. Collisson et al.   NATURE

Maturation Stage of T-cell Acute Lymphoblastic Leukemia Determines BCL-2 versus BCL-XL Dependence and Sensitivity to ABT-199

(2014) T. N. Chonghaile et al.   Cancer Discovery

Regulation of Mcl-1 Expression in Context to Bone Marrow Stromal Microenvironment in Chronic Lymphocytic Leukemia

(2014) Kumudha Balakrishnan et al.   NEOPLASIA

Targeting Mcl-1 for multiple myeloma (MM) therapy: Drug-induced generation of Mcl-1 fragment Mcl-1128–350 triggers MM cell death via c-Jun upregulation

(2013) Fengjuan Fan et al.   CANCER LETTERS

Oncogenic BRAF signalling increases Mcl-1 expression in cutaneous metastatic melanoma

(2013) Christopher S. McKee et al.   EXPERIMENTAL DERMATOLOGY

Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction

(2013) X. Wang et al.   GENES & DEVELOPMENT

The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma

(2013) C Touzeau et al.   LEUKEMIA

Mcl-1 is essential for the survival of plasma cells

(2013) Victor Peperzak et al.   NATURE IMMUNOLOGY

Molecular Profiling of the Residual Disease of Triple-Negative Breast Cancers after Neoadjuvant Chemotherapy Identifies Actionable Therapeutic Targets

(2013) J. M. Balko et al.   Cancer Discovery

Chemical Genomics Identifies Small-Molecule MCL1 Repressors and BCL-xL as a Predictor of MCL1 Dependency

(2012) Guo Wei et al.   CANCER CELL

Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia

(2012) S. P. Glaser et al.   GENES & DEVELOPMENT

Negative Regulation of the Stability and Tumor Suppressor Function of Fbw7 by the Pin1 Prolyl Isomerase

(2012) Sang-Hyun Min et al.   MOLECULAR CELL

Comprehensive genomic characterization of squamous cell lung cancers

(2012)   NATURE

Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration

(2012) Rhonda M. Perciavalle et al.   NATURE CELL BIOLOGY

Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells

(2011) A. A. Morales et al.   BLOOD

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease

(2011) Andrew W. Roberts et al.   JOURNAL OF CLINICAL ONCOLOGY

SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction

(2011) Hiroyuki Inuzuka et al.   NATURE

Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7

(2011) Ingrid E. Wertz et al.   NATURE

Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy

(2011) T. N. Chonghaile et al.   SCIENCE

MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner

(2010) Marc Germain et al.   EMBO JOURNAL

Mcl-1 Stability Determines Mitotic Cell Fate of Human Multiple Myeloma Tumor Cells Treated with the Kinesin Spindle Protein Inhibitor ARRY-520

(2010) B. J. Tunquist et al.   MOLECULAR CANCER THERAPEUTICS

The landscape of somatic copy-number alteration across human cancers

(2010) Rameen Beroukhim et al.   NATURE

FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation

(2009) G. Yoshimoto et al.   BLOOD

A novel molecular mechanism of primary resistance to FLT3-kinase inhibitors in AML

(2009) F. Breitenbuecher et al.   BLOOD

MCL-1–dependent leukemia cells are more sensitive to chemotherapy than BCL-2–dependent counterparts

(2009) Joslyn K. Brunelle et al.   JOURNAL OF CELL BIOLOGY

Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival

(2009) Martin Schwickart et al.   NATURE

Structure of the BH3 Domains from the p53-Inducible BH3-Only Proteins Noxa and Puma in Complex with Mcl-1

(2008) Catherine L. Day et al.   JOURNAL OF MOLECULAR BIOLOGY

Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B cells

(2008) S Gobessi et al.   LEUKEMIA

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

(2008) Scott M. Wilhelm et al.   MOLECULAR CANCER THERAPEUTICS