Attacking cancer's Achilles heel: antagonism of anti-apoptotic BCL-2 family members

Structure-Guided Design of a Series of MCL-1 Inhibitors with High Affinity and Selectivity

(2015) Milan Bruncko et al.   JOURNAL OF MEDICINAL CHEMISTRY

Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy

(2015) Joel D. Leverson et al.   Science Translational Medicine

Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax)

(2015) J D Leverson et al.   Cell Death & Disease

MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies

(2015) G S Choudhary et al.   Cell Death & Disease

Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma

(2015) David Chiron et al.   Oncotarget

Sabutoclax (BI97C1) and BI112D1, Putative Inhibitors of MCL-1, Induce Mitochondrial Fragmentation Either Upstream of or Independent of Apoptosis

(2015) Shankar Varadarajan et al.   NEOPLASIA

ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia

(2014) S. Peirs et al.   BLOOD

Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression

(2014) Kenichiro Doi et al.   CANCER BIOLOGY & THERAPY

The Anti-Apoptotic Bcl-2 Family Member Mcl-1 Promotes T Lymphocyte Survival at Multiple Stages

(2014) I. Dzhagalov et al.   JOURNAL OF IMMUNOLOGY

3-Substituted-N-(4-Hydroxynaphthalen-1-yl)arylsulfonamides as a Novel Class of Selective Mcl-1 Inhibitors: Structure-Based Design, Synthesis, SAR, and Biological Evaluation

(2014) Fardokht A. Abulwerdi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Activation of the Proapoptotic Bcl-2 Protein Bax by a Small Molecule Induces Tumor Cell Apoptosis

(2014) G. Zhao et al.   MOLECULAR AND CELLULAR BIOLOGY

PI3K and Bcl-2 Inhibition Primes Glioblastoma Cells to Apoptosis through Downregulation of Mcl-1 and Phospho-BAD

(2014) Fresia Pareja et al.   MOLECULAR CANCER RESEARCH

Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity

(2014) Zhi-Fu Tao et al.   ACS Medicinal Chemistry Letters

Small-molecule Bax agonists for cancer therapy

(2014) Meiguo Xin et al.   Nature Communications

ABT-199 Shows Effectiveness in CLL

(2014)   Cancer Discovery

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

The putative BH3 mimetic S1 sensitizes leukemia to ABT-737 by increasing reactive oxygen species, inducing endoplasmic reticulum stress, and upregulating the BH3-only protein NOXA

(2013) Ryan Soderquist et al.   APOPTOSIS

Hydroxyquinoline-derived compounds and analoguing of selective Mcl-1 inhibitors using a functional biomarker

(2013) David J. Richard et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia

(2013) B. Koss et al.   BLOOD

Mcl-1 antagonizes Bax/Bak to promote effector CD4+ and CD8+ T-cell responses

(2013) P Tripathi et al.   CELL DEATH AND DIFFERENTIATION

Evaluation and critical assessment of putative MCL-1 inhibitors

(2013) S Varadarajan et al.   CELL DEATH AND DIFFERENTIATION

Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure

(2013) R. L. Thomas et al.   GENES & DEVELOPMENT

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

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

A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer

(2013) William R. Schelman et al.   INVESTIGATIONAL NEW DRUGS

Pan-Mammalian Target of Rapamycin (mTOR) Inhibitor AZD8055 Primes Rhabdomyosarcoma Cells for ABT-737-induced Apoptosis by Down-regulating Mcl-1 Protein

(2013) Ellen Preuss et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Obatoclax Mesylate, a Pan–Bcl-2 Inhibitor, in Combination with Docetaxel in a Phase 1/2 Trial in Relapsed Non–Small-Cell Lung Cancer

(2013) Alberto Chiappori et al.   Journal of Thoracic Oncology

BH3 profiling in whole cells by fluorimeter or FACS

(2013) Jeremy Ryan et al.   METHODS

A Novel Small-Molecule Inhibitor of Mcl-1 Blocks Pancreatic Cancer Growth In Vitro and In Vivo

(2013) F. Abulwerdi et al.   MOLECULAR CANCER THERAPEUTICS

Structure-guided design of a selective BCL-XL inhibitor

(2013) Guillaume Lessene et al.   Nature Chemical Biology

Mcl-1 is essential for the survival of plasma cells

(2013) Victor Peperzak et al.   NATURE IMMUNOLOGY

Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells

(2013) Wim Pierson et al.   NATURE IMMUNOLOGY

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

(2013) Andrew J Souers et al.   NATURE MEDICINE

Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia

(2013) R. Pan et al.   Cancer Discovery

mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1

(2013) A. C. Faber et al.   Cancer Discovery

Targeting antiapoptotic A1/Bfl-1 by in vivo RNAi reveals multiple roles in leukocyte development in mice

(2012) E. Ottina et al.   BLOOD

A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer

(2012) A A Chiappori et al.   BRITISH JOURNAL OF CANCER

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

(2012) Guo Wei et al.   CANCER CELL

A Competitive Stapled Peptide Screen Identifies a Selective Small Molecule that Overcomes MCL-1-Dependent Leukemia Cell Survival

(2012) Nicole A. Cohen et al.   CHEMISTRY & BIOLOGY

Discovery of Marinopyrrole A (Maritoclax) as a Selective Mcl-1 Antagonist that Overcomes ABT-737 Resistance by Binding to and Targeting Mcl-1 for Proteasomal Degradation

(2012) Kenichiro Doi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Mcl-1 regulates the survival of adult neural precursor cells

(2012) Craig D. Malone et al.   MOLECULAR AND CELLULAR NEUROSCIENCE

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

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

Direct and selective small-molecule activation of proapoptotic BAX

(2012) Evripidis Gavathiotis et al.   Nature Chemical Biology

Delving deeper: MCL-1's contributions to normal and cancer biology

(2012) Rhonda M. Perciavalle et al.   TRENDS IN CELL BIOLOGY

Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer

(2011) G. Sonpavde et al.   ANNALS OF ONCOLOGY

Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets

(2011) S. M. Schoenwaelder et al.   BLOOD

Multiple BH3 Mimetics Antagonize Antiapoptotic MCL1 Protein by Inducing the Endoplasmic Reticulum Stress Response and Up-regulating BH3-only Protein NOXA

(2011) Tina C. Albershardt et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phase I Study of Navitoclax (ABT-263), a Novel Bcl-2 Family Inhibitor, in Patients With Small-Cell Lung Cancer and Other Solid Tumors

(2011) Leena Gandhi et al.   JOURNAL OF CLINICAL ONCOLOGY

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

Double-Blind, Placebo-Controlled, Randomized Phase 2 Study of the Proapoptotic Agent AT-101 Plus Docetaxel, in Second-Line Non-small Cell Lung Cancer

(2011) Neal Ready et al.   Journal of Thoracic Oncology

A Phase II Study of AT-101 (Gossypol) in Chemotherapy-Sensitive Recurrent Extensive-Stage Small Cell Lung Cancer

(2011) Maria Q. Baggstrom et al.   Journal of Thoracic Oncology

A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer

(2011) Paul K. Paik et al.   LUNG CANCER

A Unified Model of Mammalian BCL-2 Protein Family Interactions at the Mitochondria

(2011) Fabien Llambi et al.   MOLECULAR CELL

Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7

(2011) Ingrid E. Wertz et al.   NATURE

Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1

(2010) D. Yecies et al.   BLOOD

A novel BH3 mimetic S1 potently induces Bax/Bak-dependent apoptosis by targeting both Bcl-2 and Mcl-1

(2010) Zhichao Zhang et al.   INTERNATIONAL JOURNAL OF CANCER

BI-97C1, an Optically Pure Apogossypol Derivative as Pan-Active Inhibitor of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins

(2010) Jun Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity

(2010) Wyndham H Wilson et al.   LANCET ONCOLOGY

Ubiquitin-Independent Degradation of Antiapoptotic MCL-1

(2010) D. P. Stewart et al.   MOLECULAR AND CELLULAR BIOLOGY

Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia

(2008) S. M. O'Brien et al.   BLOOD

Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function

(2008) D. A. Steimer et al.   BLOOD

Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax)

(2008) M. Konopleva et al.   CANCER RESEARCH

ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor

(2008) C. Tse et al.   CANCER RESEARCH

Mcl-1 Is a Key Regulator of Apoptosis during CNS Development and after DNA Damage

(2008) N. Arbour et al.   JOURNAL OF NEUROSCIENCE

mTORC1 promotes survival through translational control of Mcl-1

(2008) J. R. Mills et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA