Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway

Sabutoclax, a Mcl-1 Antagonist, Inhibits Tumorigenesis in Transgenic Mouse and Human Xenograft Models of Prostate Cancer

(2015) Roger S. Jackson et al.   NEOPLASIA

ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia

(2013) C. J. Vandenberg et al.   BLOOD

Targeting BCL-2 with the BH3 Mimetic ABT-199 in Estrogen Receptor-Positive Breast Cancer

(2013) François Vaillant et al.   CANCER CELL

Bax Crystal Structures Reveal How BH3 Domains Activate Bax and Nucleate Its Oligomerization to Induce Apoptosis

(2013) Peter E. Czabotar et al.   CELL

Evaluation and critical assessment of putative MCL-1 inhibitors

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

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

(2013) Z Peng et al.   CELL DEATH AND DIFFERENTIATION

Obatoclax (GX15-070) triggers necroptosis by promoting the assembly of the necrosome on autophagosomal membranes

(2013) F Basit et al.   CELL DEATH AND DIFFERENTIATION

Structure-Guided Rational Design of α/β-Peptide Foldamers with High Affinity for BCL-2 Family Prosurvival Proteins

(2013) Brian J. Smith et al.   CHEMBIOCHEM

Assembly of the Bak Apoptotic Pore

(2013) Stephen Ma et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Potent and Selective Benzothiazole Hydrazone Inhibitors of Bcl-XL

(2013) Brad E. Sleebs et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Potent and Highly Efficacious Bcl-2/Bcl-xL Inhibitor

(2013) Angelo Aguilar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Bax Exists in a Dynamic Equilibrium between the Cytosol and Mitochondria to Control Apoptotic Priming

(2013) Barbara Schellenberg et al.   MOLECULAR CELL

Structure-guided design of a selective BCL-XL inhibitor

(2013) Guillaume Lessene et al.   Nature Chemical Biology

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

(2013) Andrew J Souers et al.   NATURE MEDICINE

BID-induced structural changes in BAK promote apoptosis

(2013) Tudor Moldoveanu et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Direct activation of full-length proapoptotic BAK

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

Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease

(2013) K. D. Mason et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Role of the Acidity of N-Heteroaryl Sulfonamides as Inhibitors of Bcl-2 Family Protein–Protein Interactions

(2013) B. Barry Touré et al.   ACS Medicinal Chemistry Letters

Stabilizing the Pro-Apoptotic BimBH3 Helix (BimSAHB) Does Not Necessarily Enhance Affinity or Biological Activity

(2012) Toru Okamoto et al.   ACS Chemical Biology

Stapled Peptides with Improved Potency and Specificity That Activate p53

(2012) Christopher J. Brown et al.   ACS Chemical Biology

Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists

(2012) Heidi L. Perez et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists

(2012) Gretchen M. Schroeder et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Bcl-2, Bcl-xL, and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells

(2012) D. Merino 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

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

Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer

(2012) C. M. Rudin et al.   CLINICAL CANCER RESEARCH

A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers

(2012) James L. LaBelle et al.   JOURNAL OF CLINICAL INVESTIGATION

Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold

(2012) Haibin Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression

(2012) Jianfang Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

(2012) Haibin Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design

(2012) Anders Friberg et al.   JOURNAL OF MEDICINAL CHEMISTRY

Enhancement of α-Helix Mimicry by an α/β-Peptide Foldamer via Incorporation of a Dense Ionic Side-Chain Array

(2012) Lisa M. Johnson et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Direct and selective small-molecule activation of proapoptotic BAX

(2012) Evripidis Gavathiotis et al.   Nature Chemical Biology

Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B

(2012) R W Rooswinkel et al.   Cell Death & Disease

Bcl-xL Retrotranslocates Bax from the Mitochondria into the Cytosol

(2011) Frank Edlich et al.   CELL

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Bax dimerizes via a symmetric BH3:groove interface during apoptosis

(2011) G Dewson et al.   CELL DEATH AND DIFFERENTIATION

Structural Basis of Bcl-xL Recognition by a BH3-Mimetic α/β-Peptide Generated by Sequence-Based Design

(2011) Erinna F. Lee et al.   CHEMBIOCHEM

Mutation to Bax beyond the BH3 Domain Disrupts Interactions with Pro-survival Proteins and Promotes Apoptosis

(2011) Peter E. Czabotar 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

Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity

(2011) Brad E. Sleebs et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design of Triazole-Stapled BCL9 α-Helical Peptides to Target the β-Catenin/B-Cell CLL/lymphoma 9 (BCL9) Protein–Protein Interaction

(2011) Steven A. Kawamoto et al.   JOURNAL OF MEDICINAL CHEMISTRY

Evaluation of Diverse α/β-Backbone Patterns for Functional α-Helix Mimicry: Analogues of the Bim BH3 Domain

(2011) Melissa D. Boersma et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

(2011) Fabien Llambi et al.   MOLECULAR CELL

Apogossypol derivative BI-97C1 (Sabutoclax) targeting Mcl-1 sensitizes prostate cancer cells to mda-7/IL-24-mediated toxicity

(2011) R. Dash et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Molecular biology of Bax and Bak activation and action

(2010) Dana Westphal et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Bcl-2 Family Proteins as Therapeutic Targets

(2010) Peter E. Czabotar et al.   CURRENT PHARMACEUTICAL DESIGN

Conformational Changes in BAK, a Pore-forming Proapoptotic Bcl-2 Family Member, upon Membrane Insertion and Direct Evidence for the Existence of BH3-BH3 Contact Interface in BAK Homo-oligomers

(2010) Kyoung Joon Oh et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Bax Forms an Oligomer via Separate, Yet Interdependent, Surfaces

(2010) Zhi Zhang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Regulation of the Apaf-1-caspase-9 apoptosome

(2010) S. B. Bratton et al.   JOURNAL OF CELL SCIENCE

Synthesis and Biological Evaluation of Apogossypolone Derivatives as Pan-active Inhibitors of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins

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

Phase I/II Study of AT-101 with Topotecan in Relapsed and Refractory Small Cell Lung Cancer

(2010) Rebecca Suk Heist et al.   Journal of Thoracic Oncology

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

BH3-Triggered Structural Reorganization Drives the Activation of Proapoptotic BAX

(2010) Evripidis Gavathiotis et al.   MOLECULAR CELL

Inflammatory, Apoptotic, and Survival Gene Signaling in Alzheimer’s Disease

(2010) Walter J. Lukiw et al.   MOLECULAR NEUROBIOLOGY

The landscape of somatic copy-number alteration across human cancers

(2010) Rameen Beroukhim et al.   NATURE

The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer

(2010) Michelle L Stewart et al.   Nature Chemical Biology

Still embedded together binding to membranes regulates Bcl-2 protein interactions

(2010) B Leber et al.   ONCOGENE

BH3 mimetics antagonizing restricted prosurvival Bcl-2 proteins represent another class of selective immune modulatory drugs

(2010) E. M. Carrington et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

MAC inhibitors suppress mitochondrial apoptosis

(2009) Pablo M. Peixoto et al.   BIOCHEMICAL JOURNAL

Atropisomeric small molecule Bcl-2 ligands: Determination of bioactive conformation

(2009) John Porter et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

An Open-Label, Multicenter, Phase I/II Study of Single-Agent AT-101 in Men with Castrate-Resistant Prostate Cancer

(2009) G. Liu et al.   CLINICAL CANCER RESEARCH

Apogossypol Derivatives as Pan-Active Inhibitors of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins

(2009) Jun Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

The BH3 mimetic compound, ABT-737, synergizes with a range of cytotoxic chemotherapy agents in chronic lymphocytic leukemia

(2009) K D Mason et al.   LEUKEMIA

Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins

(2009) J. Wei et al.   MOLECULAR CANCER THERAPEUTICS

Targeting post-mitochondrial effectors of apoptosis for neuroprotection

(2008) Lorenzo Galluzzi et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors

(2008) John Porter et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

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

(2008) C. Tse et al.   CANCER RESEARCH

Membrane Binding by tBid Initiates an Ordered Series of Events Culminating in Membrane Permeabilization by Bax

(2008) Jonathan F. Lovell et al.   CELL

Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands

(2008) M Kvansakul et al.   CELL DEATH AND DIFFERENTIATION

A Phase I Study of the Pan Bcl-2 Family Inhibitor Obatoclax Mesylate in Patients with Advanced Hematologic Malignancies

(2008) A. D. Schimmer et al.   CLINICAL CANCER RESEARCH

Completing the family portrait of the anti-apoptotic Bcl-2 proteins: Crystal structure of human Bfl-1 in complex with Bim

(2008) Maria Dolores Herman et al.   FEBS LETTERS

Dynamics and structure of the Bax-Bak complex responsible for releasing mitochondrial proteins during apoptosis

(2008) L. Zhou et al.   JOURNAL OF CELL SCIENCE

Synthesis and Conformational Analysis of a Cyclic Peptide Obtained viaitoi+4 Intramolecular Side-Chain to Side-Chain Azide−Alkyne 1,3-Dipolar Cycloaddition

(2008) Sonia Cantel et al.   JOURNAL OF ORGANIC CHEMISTRY

To Trigger Apoptosis, Bak Exposes Its BH3 Domain and Homodimerizes via BH3:Groove Interactions

(2008) Grant Dewson et al.   MOLECULAR CELL

BAX activation is initiated at a novel interaction site

(2008) Evripidis Gavathiotis et al.   NATURE

BCL-2 family antagonists for cancer therapy

(2008) Guillaume Lessene et al.   NATURE REVIEWS DRUG DISCOVERY

The BCL-2 protein family: opposing activities that mediate cell death

(2007) Richard J. Youle et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY