Nature Search

Re-appraising assays on permeabilized blood cancer cells testing venetoclax or other BH3 mimetic agents selectively targeting pro-survival BCL2 proteins

Jia-Nan Gong
Tirta M. Djajawi
David C. S. Huang
ResearchOpen Access09 Apr 2025
Cell Death & Differentiation

P: 1-15
A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Stefanie M. Bader
Dale J. Calleja
David Komander
ResearchOpen Access03 Apr 2025
Nature Communications

Volume: 16, P: 1-20
The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells

Zilu Wang
Huimin Hu
Andreas Strasser
ResearchOpen Access04 Feb 2023
Cell Death & Differentiation

Volume: 30, P: 1033-1046
A small molecule interacts with VDAC2 to block mouse BAK-driven apoptosis

A phenotypic screen led to the identification of potent inhibitors of mouse BAK-driven apoptosis. The compounds interact with VDAC2 and stabilize its interaction with BAK, blocking apoptosis at an early stage to preserve long-term cell survival.

Mark F. van Delft
Stephane Chappaz
Benjamin T. Kile
Research07 Oct 2019
Nature Chemical Biology

Volume: 15, P: 1057-1066
BCL-2 family antagonists for cancer therapy

The pro-survival BCL-2 family of proteins provides exciting drug targets for the selective induction of apoptosis in cancer cells, in which these proteins are often overexpressed. Lessene and colleagues review the preclinical and clinical data for BCL-2 antagonists, and recommend criteria for establishing the mode of action for this new drug class.

Guillaume Lessene
Peter E. Czabotar
Peter M. Colman
Reviews01 Dec 2008
Nature Reviews Drug Discovery

Volume: 7, P: 989-1000
A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

Receptor Interacting Protein Kinase 2 (RIPK2) mediates innate immune signalling in response to intracellular pathogens, but its aberrant activation contributes to autoimmune pathologies. Here Nachbur et al.describe a RIPK2 inhibitor that is effective in a mouse model of multiple sclerosis.

Ueli Nachbur
Che A. Stafford
John Silke
Research17 Mar 2015
Nature Communications

Volume: 6, P: 1-13
Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape

Analysis of over 6000 single-site variants of SARS-CoV-2 Papain-Like protease uncovers critical mutations involved in enzymatic function and highlight the potential for drug-escape.

Xinyu Wu
Margareta Go
Melissa J. Call
ResearchOpen Access23 Jul 2024
Nature Communications

Volume: 15, P: 1-18
Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy

Interactions on the mitochondrial outer membrane between members of the three subgroups of the BCL-2 protein family set the apoptotic threshold. Recent structural insights into the molecular mechanisms of this commitment to apoptosis are guiding the development of new therapeutics for cancer, and potentially also autoimmune and infectious diseases.

Peter E. Czabotar
Guillaume Lessene
Jerry M. Adams
Reviews20 Dec 2013
Nature Reviews Molecular Cell Biology

Volume: 15, P: 49-63
Correction to: The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells

Zilu Wang
Huimin Hu
Andreas Strasser
Amendments and CorrectionsOpen Access24 Feb 2023
Cell Death & Differentiation

Volume: 30, P: 1096
BH3 mimetic drugs cooperate with Temozolomide, JQ1 and inducers of ferroptosis in killing glioblastoma multiforme cells

Diane Moujalled
Adam G. Southon
Andreas Strasser
Research24 Mar 2022
Cell Death & Differentiation

Volume: 29, P: 1335-1348
Development of NanoLuc-targeting protein degraders and a universal reporter system to benchmark tag-targeted degradation platforms

tag-Targeted Protein Degrader (tTPD) systems are powerful tools for preclinical target validation. Here the authors extend the tTPD platform by developing NanoTACs that degrade NanoLuc tagged substrates and benchmark each tTPD system using an interchangeable tag reporter system.

Christoph Grohmann
Charlene M. Magtoto
Rebecca Feltham
ResearchOpen Access19 Apr 2022
Nature Communications

Volume: 13, P: 1-13
Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations

The BCL-2 mutation G101V reduces venetoclax affinity and confers drug resistance in patients with chronic lymphocytic leukaemia. Here, the authors present crystal structures and biochemical analyses of venetoclax bound to BCL-2 and the G101V mutant, revealing the structural basis for venetoclax resistance.

Richard W. Birkinshaw
Jia-nan Gong
Peter E. Czabotar
ResearchOpen Access03 Jun 2019
Nature Communications

Volume: 10, P: 1-10
Human RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis

The pseudokinase MLKL is activated by the upstream kinase RIPK3 in the necroptotic pathway but the structural basis of MLKL activation is not well understood yet. Here, the authors present the crystal structures of the human RIPK3:MLKL complex and human RIPK3 kinase alone, which reveal structural differences between human and murine RIPK3 and they discuss mechanistic implications.

Yanxiang Meng
Katherine A. Davies
James M. Murphy
ResearchOpen Access22 Nov 2021
Nature Communications

Volume: 12, P: 1-15
MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis

Mixed lineage kinase ___domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. Here the authors show that MLKL trafficking and plasma membrane accumulation are crucial necroptosis checkpoints, and that accumulation of phosphorylated MLKL at intercellular junctions promotes necroptosis.

Andre L. Samson
Ying Zhang
James M. Murphy
ResearchOpen Access19 Jun 2020
Nature Communications

Volume: 11, P: 1-17
Conformational switching of the pseudokinase ___domain promotes human MLKL tetramerization and cell death by necroptosis

RIPK3-mediated phosphorylation of the mixed lineage kinase ___domain-like (MLKL) pseudokinase is thought to be the trigger for MLKL activation during necroptotic signaling. Here the authors provide evidence that the transition of human MLKL from a monomeric state to a tetramer is essential for necroptosis signalling.

Emma J. Petrie
Jarrod J. Sandow
James M. Murphy
ResearchOpen Access21 Jun 2018
Nature Communications

Volume: 9, P: 1-15
The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

S63845 specifically inhibits MCL1 and induces tumour cell death in vitro and in vivo in diverse cancer-derived cell lines with an acceptable safety margin.

András Kotschy
Zoltán Szlavik
Olivier Geneste
Research19 Oct 2016
Nature

Volume: 538, P: 477-482
Structure-guided design of a selective BCL-X_L inhibitor

A high-throughput chemical screen followed by structure-guided chemical design leads to the first potent and selective small-molecule BCL-X_L inhibitor.

Guillaume Lessene
Peter E Czabotar
Keith G Watson
Research21 Apr 2013
Nature Chemical Biology

Volume: 9, P: 390-397
Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis

Inhibition of BCL-XL eliminates Legionella infection, suggesting that host-directed BH3-mimetic therapy may be effective against intracellular pathogens that inhibit host cell protein synthesis.

Mary Speir
Kate E. Lawlor
Thomas Naderer
Research24 Feb 2016
Nature Microbiology

Volume: 1, P: 1-9
Preclinical small molecule WEHI-7326 overcomes drug resistance and elicits response in patient-derived xenograft models of human treatment-refractory tumors

Christoph Grohmann
Francesca Walker
Guillaume Lessene
ResearchOpen Access12 Mar 2021
Cell Death & Disease

Volume: 12, P: 1-18
The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs

BH3-mimetic drugs have been designed to directly induce apoptosis in cancer cells by targeting prosurvival BCL-2 family proteins. This Review discusses their continued development and the challenges arising from their implementation in the clinic, such as resistance or on-target toxic effects, and the approaches that could be harnessed to overcome these obstacles.

Sarah T. Diepstraten
Mary Ann Anderson
Gemma L. Kelly
Reviews18 Oct 2021
Nature Reviews Cancer

Volume: 22, P: 45-64
The Lck inhibitor, AMG-47a, blocks necroptosis and implicates RIPK1 in signalling downstream of MLKL

Annette V. Jacobsen
Catia L. Pierotti
James M. Murphy
ResearchOpen Access01 Apr 2022
Cell Death & Disease

Volume: 13, P: 1-13
Dual inhibition of BCL-XL and MCL-1 is required to induce tumour regression in lung squamous cell carcinomas sensitive to FGFR inhibition

Clare E. Weeden
Casey Ah-Cann
Marie-Liesse Asselin-Labat
Research10 May 2018
Oncogene

Volume: 37, P: 4475-4488
Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia

Donia M. Moujalled
Giovanna Pomilio
Andrew H. Wei
ResearchOpen Access10 Sept 2018
Leukemia

Volume: 33, P: 905-917
Removal of BFL-1 sensitises some melanoma cells to killing by BH3 mimetic drugs

Lahiru Gangoda
Robyn L. Schenk
Marco J. Herold
Comments & OpinionOpen Access04 Apr 2022
Cell Death & Disease

Volume: 13, P: 1-3
Defining the susceptibility of colorectal cancers to BH3-mimetic compounds

Ming-Jie Luo
Michelle Palmieri
Jia-nan Gong
Comments & OpinionOpen Access10 Sept 2020
Cell Death & Disease

Volume: 11, P: 1-4
Hepatocyte growth factor renders BRAF mutant human melanoma cell lines resistant to PLX4032 by downregulating the pro-apoptotic BH3-only proteins PUMA and BIM

Leona Rohrbeck
Jia-Nan Gong
Marco J Herold
Research30 Sept 2016
Cell Death & Differentiation

Volume: 23, P: 2054-2062
The BH3-only proteins BIM and PUMA are not critical for the reticulocyte apoptosis caused by loss of the pro-survival protein BCL-XL

Alex RD Delbridge
Brandon J Aubrey
Stephanie Grabow
ResearchOpen Access06 Jul 2017
Cell Death & Disease

Volume: 8, P: e2914

Search

Re-appraising assays on permeabilized blood cancer cells testing venetoclax or other BH3 mimetic agents selectively targeting pro-survival BCL2 proteins

A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID

The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells

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

BCL-2 family antagonists for cancer therapy

A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape

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

Correction to: The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells

BH3 mimetic drugs cooperate with Temozolomide, JQ1 and inducers of ferroptosis in killing glioblastoma multiforme cells

Development of NanoLuc-targeting protein degraders and a universal reporter system to benchmark tag-targeted degradation platforms

Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations

Human RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis

MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis

Conformational switching of the pseudokinase ___domain promotes human MLKL tetramerization and cell death by necroptosis

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

Structure-guided design of a selective BCL-X_L inhibitor

Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis

Preclinical small molecule WEHI-7326 overcomes drug resistance and elicits response in patient-derived xenograft models of human treatment-refractory tumors

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

The Lck inhibitor, AMG-47a, blocks necroptosis and implicates RIPK1 in signalling downstream of MLKL

Dual inhibition of BCL-XL and MCL-1 is required to induce tumour regression in lung squamous cell carcinomas sensitive to FGFR inhibition

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

Removal of BFL-1 sensitises some melanoma cells to killing by BH3 mimetic drugs

Defining the susceptibility of colorectal cancers to BH3-mimetic compounds

Hepatocyte growth factor renders BRAF mutant human melanoma cell lines resistant to PLX4032 by downregulating the pro-apoptotic BH3-only proteins PUMA and BIM

The BH3-only proteins BIM and PUMA are not critical for the reticulocyte apoptosis caused by loss of the pro-survival protein BCL-XL

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