Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers

Design and optimisation of dendrimer-conjugated Bcl-2/xL inhibitor, AZD0466, with improved therapeutic index for cancer therapy

(2021) Claire M. Patterson et al.   Communications Biology

Inhibitors of BCL2A1/Bfl-1 Protein: Potential Stock in Cancer Therapy

(2021) Xue Li et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A Phase I study of the safety, pharmacokinetics and efficacy of navitoclax plus docetaxel in patients with advanced solid tumors

(2021) Martina Puglisi et al.   Future Oncology

A first-in-human study of mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose escalation results.

(2021) Anthony W. Tolcher et al.   JOURNAL OF CLINICAL ONCOLOGY

Dynamic BH3 profiling identifies active BH3 mimetic combinations in non-small cell lung cancer

(2021) Danielle S. Potter et al.   Cell Death & Disease

A novel BH3-mimetic, AZD0466, targeting BCL-XL and BCL-2 is effective in pre-clinical models of malignant pleural mesothelioma

(2021) Surein Arulananda et al.   Cell Death Discovery

Targeting MCL-1 in hematologic malignancies: Rationale and progress

(2020) AndrewH. Wei et al.   BLOOD REVIEWS

STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment

(2020) Steven Lohard et al.   Nature Communications

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

(2020) Shanshan Pei et al.   Cancer Discovery

Co‐targeting bromodomain and extra‐terminal proteins and MCL1 induces synergistic cell death in melanoma

(2020) Hsin‐Yi Tseng et al.   INTERNATIONAL JOURNAL OF CANCER

First-in-human study of palcitoclax (APG-1252), a novel dual Bcl-2/Bcl-xL inhibitor, demonstrated advantages in platelet safety while maintaining anticancer effect in U.S. patients with metastatic solid tumors.

(2020) Nehal J. Lakhani et al.   JOURNAL OF CLINICAL ONCOLOGY

Combined reduction in the expression of MCL-1 and BCL-2 reduces organismal size in mice

(2020) Francine Ke et al.   Cell Death & Disease

Discovery of A-1331852, a First-in-Class, Potent and Orally-Bioavailable BCL-XL Inhibitor

(2020) Le Wang et al.   ACS Medicinal Chemistry Letters

Bcl‐2/Bcl‐xl inhibitor APG‐1252‐M1 is a promising therapeutic strategy for gastric carcinoma

(2020) Hanjie Yi et al.   Cancer Medicine

MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells

(2020) Nabanita Mukherjee et al.   Cell Death & Disease

Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma

(2020) Nabanita Mukherjee et al.   Cancers

B7-H3: an attractive target for antibody-based immunotherapy

(2020) Filippos Kontos et al.   CLINICAL CANCER RESEARCH

Defining the susceptibility of colorectal cancers to BH3-mimetic compounds

(2020) Ming-Jie Luo et al.   Cell Death & Disease

Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance

(2020) Clara Alcon et al.   Cell Death & Disease

Targeting Bfl-1 via acute CDK9 inhibition overcomes intrinsic BH3 mimetic resistance in lymphomas

(2020) Scott Boiko et al.   BLOOD

Targeting MCL-1 dysregulates cell metabolism and leukemia-stroma interactions and resensitizes acute myeloid leukemia to BCL-2 inhibition

(2020) Bing Z. Carter et al.   HAEMATOLOGICA

Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies

(2020) Bernard Barlaam et al.   JOURNAL OF MEDICINAL CHEMISTRY

BH3 mimetics potentiate pro-apoptotic activity of encorafenib in BRAFV600E melanoma cells

(2020) Mariusz L. Hartman et al.   CANCER LETTERS

Novel Synergistic Combination of Mitotic Arrest and Promotion of Apoptosis for Treatment of Pancreatic Adenocarcinoma

(2019) Zhijian Duan et al.   Translational Oncology

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

Genetic characterization of ABT-199 sensitivity in human AML

(2019) Richard Bisaillon et al.   LEUKEMIA

Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions

(2019) Kirsten Fischer et al.   NEW ENGLAND JOURNAL OF MEDICINE

BET inhibition as a rational therapeutic strategy for invasive lobular breast cancer

(2019) Louise Walsh et al.   CLINICAL CANCER RESEARCH

447PDPhase I/II study of combined BCL-XL and MEK inhibition with navitoclax (N) and trametinib (T) in KRAS or NRAS mutant advanced solid tumours

(2019) R B Corcoran et al.   ANNALS OF ONCOLOGY

Novel cyclin-dependent kinase 9 (CDK9) inhibitor with suppression of cancer stemness activity against non-small-cell lung cancer

(2019) Xin Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Mesothelioma cells depend on the anti-apoptotic protein Bcl-xL for survival and are sensitized to ionizing radiation by BH3-mimetics

(2019) Mark R. Jackson et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer

(2019) Braicu et al.   Cancers

A novel CDK9 inhibitor increases the efficacy of venetoclax (ABT-199) in multiple models of hematologic malignancies

(2019) Darren C. Phillips et al.   LEUKEMIA

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

(2019) Sajid Khan et al.   NATURE MEDICINE

BCL-x L -selective BH3 mimetic sensitizes rhabdomyosarcoma cells to chemotherapeutics by activation of the mitochondrial pathway of apoptosis

(2018) Sara Fatima Faqar-Uz-Zaman et al.   CANCER LETTERS

Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis

(2018) Seiji Arai et al.   CLINICAL CANCER RESEARCH

Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies

(2018) Andrew E Place et al.   Future Oncology

Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia

(2018) John F. Seymour et al.   NEW ENGLAND JOURNAL OF MEDICINE

BCL-2 selective inhibitor ABT-199 primes rhabdomyosarcoma cells to histone deacetylase inhibitor-induced apoptosis

(2018) Ulrike Heinicke et al.   ONCOGENE

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

(2018) Clare E. Weeden et al.   ONCOGENE

Systematic mapping of BCL-2 gene dependencies in cancer reveals molecular determinants of BH3 mimetic sensitivity

(2018) Ryan S. Soderquist 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

AMG 176, a Selective MCL1 Inhibitor, is Effective in Hematological Cancer Models Alone and in Combination with Established Therapies

(2018) Sean Caenepeel 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

Targeting BCL-xL improves the efficacy of bromodomain and extra-terminal protein inhibitors in triple-negative breast cancer by eliciting the death of senescent cells

(2018) Sylvia S. Gayle et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

Cyclin-dependent kinase 9 (CDK9) is a novel prognostic marker and therapeutic target in osteosarcoma

(2018) Hangzhan Ma et al.   EBioMedicine

BCL-W has a fundamental role in B cell survival and lymphomagenesis

(2017) Clare M. Adams et al.   JOURNAL OF CLINICAL INVESTIGATION

Vulnerability of Small-Cell Lung Cancer to Apoptosis Induced by the Combination of BET Bromodomain Proteins and BCL2 Inhibitors

(2017) Lloyd T. Lam et al.   MOLECULAR CANCER THERAPEUTICS

Allosteric sensitization of proapoptotic BAX

(2017) Jonathan R Pritz et al.   Nature Chemical Biology

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

CDK9 is a prognostic marker and therapeutic target in pancreatic cancer

(2017) Anna-Laura Kretz et al.   TUMOR BIOLOGY

Positive transcription elongation factor b (P-TEFb) is a therapeutic target in human multiple myeloma

(2017) Yu Zhang et al.   Oncotarget

JQ1 synergizes with the Bcl-2 inhibitor ABT-263 against MYCN-amplified small cell lung cancer

(2017) Huogang Wang et al.   Oncotarget

Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition

(2017) Joyoti Dey et al.   Scientific Reports

Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells

(2016) Shao Xie et al.   ACTA PHARMACOLOGICA SINICA

Select Bcl-2 antagonism restores chemotherapy sensitivity in high-risk neuroblastoma

(2016) Rachel Tanos et al.   BMC CANCER

Exploitation of the Apoptosis-Primed State of MYCN-Amplified Neuroblastoma to Develop a Potent and Specific Targeted Therapy Combination

(2016) Jungoh Ham et al.   CANCER CELL

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

(2016) Leona Rohrbeck et al.   CELL DEATH AND DIFFERENTIATION

Inactivation of prosurvival Bcl-2 proteins activates Bax/Bak through the outer mitochondrial membrane

(2016) Katelyn L. O'Neill et al.   GENES & DEVELOPMENT

Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods

(2016) Nicholas F. Pelz et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2016) András Kotschy et al.   NATURE

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer

(2016) Shaokun Shu et al.   NATURE

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

(2016) G. R. Anderson et al.   Science Translational Medicine

High efficacy of the BCL-2 inhibitor ABT199 (venetoclax) in BCL-2 high-expressing neuroblastoma cell lines and xenografts and rational for combination with MCL-1 inhibition

(2016) Laurel T. Bate-Eya et al.   Oncotarget

Myeloid cell leukemia-1 is an important apoptotic survival factor in triple-negative breast cancer

(2015) C M Goodwin et al.   CELL DEATH AND DIFFERENTIATION

The BCL-2 protein family, BH3-mimetics and cancer therapy

(2015) A R D Delbridge et al.   CELL DEATH AND DIFFERENTIATION

Mcl-1 antagonism is a potential therapeutic strategy in a subset of solid cancers

(2015) Michele Modugno et al.   EXPERIMENTAL CELL RESEARCH

Constitutive BAK activation as a determinant of drug sensitivity in malignant lymphohematopoietic cells

(2015) Haiming Dai et al.   GENES & DEVELOPMENT

Role of the pro-survival molecule Bfl-1 in melanoma

(2015) C.K. Hind et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Genomic analysis and selective small molecule inhibition identifies BCL-XL as a critical survival factor in a subset of colorectal cancer

(2015) Haichao Zhang et al.   Molecular Cancer

MCL-1 Is a Key Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency Utilizing a Highly Selective Small Molecule Inhibitor

(2015) Y. Xiao et al.   MOLECULAR CANCER THERAPEUTICS

Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

(2015) Anthony C. Faber et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

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

MiR-133b regulates bladder cancer cell proliferation and apoptosis by targeting Bcl-w and Akt1

(2014) Xiao-nan Chen et al.   Cancer Cell International

A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors

(2014) James M. Cleary et al.   INVESTIGATIONAL NEW DRUGS

The Epigenetic Regulator I-BET151 Induces BIM-Dependent Apoptosis and Cell Cycle Arrest of Human Melanoma Cells

(2014) Stuart J. Gallagher et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Synthetic lethality by co-targeting mitochondrial apoptosis and PI3K/Akt/mTOR signaling

(2014) Simone Fulda   MITOCHONDRION

Targeting Bcl-2/Bcl-XL Induces Antitumor Activity in Uveal Melanoma Patient-Derived Xenografts

(2014) Fariba Némati et al.   PLoS One

BM-1197: A Novel and Specific Bcl-2/Bcl-xL Inhibitor Inducing Complete and Long-Lasting Tumor Regression In Vivo

(2014) Longchuan Bai et al.   PLoS One

Bcl-xL controls a switch between cell death modes during mitotic arrest

(2014) N Bah et al.   Cell Death & Disease

Cyclin dependent kinase-9 mediated transcriptional de-regulation of cMYC as a critical determinant of endocrine-therapy resistance in breast cancers

(2013) Surojeet Sengupta et al.   BREAST CANCER RESEARCH AND TREATMENT

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

(2013) François Vaillant et al.   CANCER 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

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

BCL2A1is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition

(2013) Rizwan Haq et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Mcl-1 and Bcl-xL coordinately regulate megakaryocyte survival

(2012) M. A. Debrincat et al.   BLOOD

Synthetic Lethal Interaction of Combined BCL-XL and MEK Inhibition Promotes Tumor Regressions in KRAS Mutant Cancer Models

(2012) Ryan B. Corcoran et al.   CANCER CELL

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

Novel Therapeutic Approaches for Small Cell Lung Cancer: The Future has Arrived

(2012) Maria Catherine Pietanza et al.   CURRENT PROBLEMS IN CANCER

Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth

(2012) Fieke Lamers et al.   EUROPEAN JOURNAL OF CANCER

Navitoclax (ABT-263) Reduces Bcl-xL-Mediated Chemoresistance in Ovarian Cancer Models

(2012) M. Wong et al.   MOLECULAR CANCER THERAPEUTICS

Selective Induction of Cell Death in Melanoma Cell Lines through Targeting of Mcl-1 and A1

(2012) Daniela Senft et al.   PLoS One

ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity

(2012) Y Shao et al.   Cell Death & Disease

BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc

(2011) Jake E. Delmore et al.   CELL

Expression analysis and molecular targeting of cyclin-dependent kinases in advanced melanoma

(2011) Christopher Abdullah et al.   CELL CYCLE

Modulation of NOXA and MCL-1 as a Strategy for Sensitizing Melanoma Cells to the BH3-Mimetic ABT-737

(2011) K. M. Lucas et al.   CLINICAL CANCER RESEARCH

Navitoclax Enhances the Efficacy of Taxanes in Non–Small Cell Lung Cancer Models

(2011) Nguyen Tan et al.   CLINICAL CANCER RESEARCH

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

The Bcl-2/Bcl-XL/Bcl-w Inhibitor, Navitoclax, Enhances the Activity of Chemotherapeutic Agents In Vitro and In Vivo

(2011) J. Chen et al.   MOLECULAR CANCER THERAPEUTICS

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

Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

(2011) Mark A. Dawson et al.   NATURE

Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer

(2011) E P Booy et al.   ONCOGENE

Sensitization of BCL-2-expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737

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

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

(2010) D. Yecies et al.   BLOOD

BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received

(2010) S-J Dawson et al.   BRITISH JOURNAL OF CANCER

The landscape of somatic copy-number alteration across human cancers

(2010) Rameen Beroukhim et al.   NATURE

Mcl-1 is critical for survival in a subgroup of non-small-cell lung cancer cell lines

(2010) H Zhang et al.   ONCOGENE

MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer

(2009) Melissa Crawford et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver

(2009) Hayato Hikita et al.   HEPATOLOGY

Cyclin-Dependent Kinase 1-Mediated Bcl-xL/Bcl-2 Phosphorylation Acts as a Functional Link Coupling Mitotic Arrest and Apoptosis

(2009) D. T. Terrano et al.   MOLECULAR AND CELLULAR BIOLOGY

MYC-induced myeloid leukemogenesis is accelerated by all six members of the antiapoptotic BCL family

(2009) L J Beverly et al.   ONCOGENE

Modeling Genomic Diversity and Tumor Dependency in Malignant Melanoma

(2008) W. M. Lin et al.   CANCER RESEARCH

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

(2008) C. Tse et al.   CANCER RESEARCH

Therapeutic Efficacy of ABT-737, a Selective Inhibitor of BCL-2, in Small Cell Lung Cancer

(2008) C. L. Hann et al.   CANCER RESEARCH

Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models

(2008) A. R. Shoemaker et al.   CLINICAL CANCER RESEARCH

Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic

(2008) Mark S. Cragg et al.   JOURNAL OF CLINICAL INVESTIGATION