4.7 Article

Small molecule SJ572946 activates BAK to initiate apoptosis

Related references

Note: Only part of the references are listed.
Article Multidisciplinary Sciences

Structural basis of BAK activation in mitochondrial apoptosis initiation

Geetika Singh et al.

Summary: The study investigates the activation mechanism of BAK protein in mitochondrial apoptosis, finding that direct activation by BH3-only protein BID and BAK autoactivation cooperatively trigger BAK by BH3 ligands. This provides a unified basis for understanding how BAK is triggered by BH3 ligands.

NATURE COMMUNICATIONS (2022)

Review Oncology

The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs

Sarah T. Diepstraten et al.

Summary: Apoptosis is a programmed cell death regulated by BCL-2 family proteins. BH3-mimetic drugs have been developed to target prosurvival proteins in cancer cells. These drugs are designed to induce apoptosis and have shown efficacy in certain cancers but faces challenges like resistance and toxic effects.

NATURE REVIEWS CANCER (2022)

Review Pharmacology & Pharmacy

Evaluating and evolving a screening library in academia: the St Jude approach

Gisele Nishiguchi et al.

Summary: The quality of lead compounds is crucial for the success of chemical probe and drug discovery programs, especially with high-throughput screening being a dominant lead generation paradigm. This article discusses a strategy implemented a decade ago to build one of the largest compound collections in academia, and a recent multidisciplinary effort aimed at enhancing and expanding the collection.

DRUG DISCOVERY TODAY (2021)

Article Oncology

Venetoclax and navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Vinod A. Pullarkat et al.

Summary: In this phase I study, combining venetoclax with low-dose navitoclax and chemotherapy showed good tolerability and promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes, even in those who had failed stem cell transplant therapies.

CANCER DISCOVERY (2021)

Article Multidisciplinary Sciences

Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity

Dongwen Lv et al.

Summary: PROTACs have emerged as an innovative drug development platform with the potential to target specific proteins for degradation. Computational modeling has revealed that the accessibility of lysines on a target protein plays a crucial role in determining the selectivity and potency of PROTACs. The development of a dual degrader targeting BCL-xL and BCL-2 shows significantly improved antitumor activity, highlighting the importance of understanding target protein structure in PROTAC design.

NATURE COMMUNICATIONS (2021)

Article Chemistry, Medicinal

Pharmacological Targeting of Executioner Proteins: Controlling Life and Death

Justin P. Pogmore et al.

Summary: Although Venetoclax has achieved success in treating lymphoid malignancies by targeting the antiapoptotic protein BCL-2, there is still a need for improved targeting of pro-apoptotic proteins such as BAX, BAK, and BOK. Recent research indicates that small molecule tool compounds can positively or negatively regulate these proteins, affecting the regulation of apoptosis.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Structure of detergent-activated BAK dimers derived from the inert monomer

Richard W. Birkinshaw et al.

Summary: A body of data supports the presence of core dimers of BAK and BAX in their oligomeric, membrane-perturbing conformation, with the crystal structure of BAK α2-α8 dimers revealing extended latch domains. The data provide direct evidence for the conformational change of BAK from inert monomer to functional dimer, which is the smallest functional unit described so far.

MOLECULAR CELL (2021)

Review Hematology

BCL2 and MCL1 inhibitors for hematologic malignancies

Andrew W. Roberts et al.

Summary: BH3 mimetics are a new class of anticancer drugs that target prosurvival BCL2 proteins to induce apoptosis, with Venetoclax being the first approved BCL2 inhibitor showing activity in various lymphoid and myeloid neoplasms. Long-term exposure may lead to secondary resistance. Success of BCL2 inhibitors has led to development of BH3 mimetics targeting MCL1, with promising preclinical activity but potential challenges due to MCL1's physiological roles in nonhematologic tissues.

BLOOD (2021)

Article Biochemistry & Molecular Biology

High-resolution analysis of the conformational transition of pro-apoptotic Bak at the lipid membrane

Laura E. Sperl et al.

Summary: The study used NMR and HDX-MS techniques in lipid nanodiscs to investigate the high-resolution structural changes of Bak in a membrane environment, providing important insights into Bak-mediated membrane permeabilization. Experimental results showed that the alpha-helix 1 element in Bak is a metastable structure contributing to its pro-apoptotic features.

EMBO JOURNAL (2021)

Article Biochemistry & Molecular Biology

Dynamic reconfiguration of pro-apoptotic BAK on membranes

Jarrod J. Sandow et al.

Summary: In this study, the dynamic structural mechanisms of BAK activation on a membrane were explored using HDX-MS. It was found that the BH4 domain maintains the inactive conformation of BAK, and the N-terminal region becomes disordered post-activation without affecting its membrane permeabilization. These findings provide new insights into the potential therapeutic targeting opportunities for BAK activation.

EMBO JOURNAL (2021)

Article Medicine, Research & Experimental

Discovery of Small Molecule Bak Activator for Lung Cancer Therapy

Dongkyoo Park et al.

Summary: The proapoptotic protein Bak is a potential target for lung cancer therapy, with the BH3 domain being crucial for Bak activation. Screening identified a small molecule Bak activator, BKA-073, which effectively suppressed lung cancer cell growth and reversed radioresistance.

THERANOSTICS (2021)

Article Cell Biology

BAX, BAK, and BOK: A Coming of Age for the BCL-2 Family Effector Proteins

Tudor Moldoveanu et al.

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2020)

Article Biochemistry & Molecular Biology

BAK core dimers bind lipids and can be bridged by them

Angus D. Cowan et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

Article Education, Scientific Disciplines

Therapeutic development and current uses of BCL-2 inhibition

Andrew W. Roberts

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM (2020)

Review Biochemistry & Molecular Biology

Pore formation in regulated cell death

Hector Flores-Romero et al.

EMBO JOURNAL (2020)

Article Biochemical Research Methods

Bax to the future - A novel, high-yielding approach for purification and expression of full-length Bax protein for structural studies

Artur P. G. Dingeldein et al.

PROTEIN EXPRESSION AND PURIFICATION (2019)

Article Biochemistry & Molecular Biology

A small molecule interacts with VDAC2 to block mouse BAK-driven apoptosis

Mark F. van Delft et al.

NATURE CHEMICAL BIOLOGY (2019)

Review Cell Biology

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

Rumani Singh et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2019)

Article Biochemistry & Molecular Biology

A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity

Sajid Khan et al.

NATURE MEDICINE (2019)

Article Cell Biology

Intrinsic Instability of BOK Enables Membrane Permeabilization in Apoptosis

Janet H. Zheng et al.

CELL REPORTS (2018)

Review Oncology

BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines

Delphine Merino et al.

CANCER CELL (2018)

Review Biochemistry & Molecular Biology

BCL-2 family proteins: changing partners in the dance towards death

Justin Kale et al.

CELL DEATH AND DIFFERENTIATION (2018)

Article Biochemistry & Molecular Biology

Conversion of Bim-BH3 from Activator to Inhibitor of Bak through Structure-Based Design

Jason M. Brouwer et al.

MOLECULAR CELL (2017)

Review Biotechnology & Applied Microbiology

From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors

Avi Ashkenazi et al.

NATURE REVIEWS DRUG DISCOVERY (2017)

Article Biochemistry & Molecular Biology

Small molecules reveal an alternative mechanism of Bax activation

Hetal Brahmbhatt et al.

BIOCHEMICAL JOURNAL (2016)

Article Biochemistry & Molecular Biology

CcpNmr AnalysisAssign: a flexible platform for integrated NMR analysis

Simon P. Skinner et al.

JOURNAL OF BIOMOLECULAR NMR (2016)

Article Multidisciplinary Sciences

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

Andras Kotschy et al.

NATURE (2016)

Article Multidisciplinary Sciences

Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies

Sweta Iyer et al.

NATURE COMMUNICATIONS (2016)

Review Oncology

Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies

Alex R. D. Delbridge et al.

NATURE REVIEWS CANCER (2016)

Article Multidisciplinary Sciences

Discovery of Small Molecules that Inhibit the Disordered Protein, p27Kip1

Luigi I. Iconaru et al.

SCIENTIFIC REPORTS (2015)

Article Chemistry, Multidisciplinary

Identification of Inhibitors Against BAK Pore Formation using an Improved in vitro Assay System

Seong-Soo Song et al.

BULLETIN OF THE KOREAN CHEMICAL SOCIETY (2014)

Article Biochemistry & Molecular Biology

Organization of the Mitochondrial Apoptotic BAK Pore OLIGOMERIZATION OF THE BAK HOMODIMERS

Sreevidya Aluvila et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Article Biochemistry & Molecular Biology

Bak Core and Latch Domains Separate during Activation, and Freed Core Domains Form Symmetric Homodimers

Jason M. Brouwer et al.

MOLECULAR CELL (2014)

Review Cell Biology

Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy

Peter E. Czabotar et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2014)

Review Biochemistry & Molecular Biology

Many players in BCL-2 family affairs

Tudor Moldoveanu et al.

TRENDS IN BIOCHEMICAL SCIENCES (2014)

Article Biochemistry & Molecular Biology

Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents

Xuliang Lang et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2013)

Article Biotechnology & Applied Microbiology

A new method to customize protein expression vectors for fast, efficient and background free parallel cloning

Judith Scholz et al.

BMC BIOTECHNOLOGY (2013)

Article Biochemistry & Molecular Biology

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

Andrew J. Souers et al.

NATURE MEDICINE (2013)

Article Biochemistry & Molecular Biology

BID-induced structural changes in BAK promote apoptosis

Tudor Moldoveanu et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2013)

Article Multidisciplinary Sciences

Direct activation of full-length proapoptotic BAK

Elizaveta S. Leshchiner et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Biochemistry & Molecular Biology

Bax dimerizes via a symmetric BH3:groove interface during apoptosis

G. Dewson et al.

CELL DEATH AND DIFFERENTIATION (2012)

Article Chemistry, Multidisciplinary

Accelerated NMR Spectroscopy by Using Compressed Sensing

Krzysztof Kazimierczuk et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2011)

Review Biochemistry & Molecular Biology

Hallmarks of Cancer: The Next Generation

Douglas Hanahan et al.

Article Biochemistry & Molecular Biology

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

Fabien Llambi et al.

MOLECULAR CELL (2011)

Review Biochemistry & Molecular Biology

The BCL-2 Family Reunion

Jerry E. Chipuk et al.

MOLECULAR CELL (2010)

Article Biochemistry & Molecular Biology

Bak Activation for Apoptosis Involves Oligomerization of Dimers via Their α6 Helices

Grant Dewson et al.

MOLECULAR CELL (2009)

Article Oncology

ABT-263: A potent and orally bioavailable Bcl-2 family inhibitor

Christin Tse et al.

CANCER RESEARCH (2008)

Article Biochemistry & Molecular Biology

To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3: Groove interactions

Grant Dewson et al.

MOLECULAR CELL (2008)

Article Biochemical Research Methods

Cell-free analysis of tail-anchor protein targeting to membranes

Matthew P. A. Henderson et al.

METHODS (2007)

Article Biochemistry & Molecular Biology

The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site

Tudor Moldoveanu et al.

MOLECULAR CELL (2006)