Strategies to Reduce the On‐Target Platelet Toxicity of Bcl‐x L Inhibitors: PROTACs, SNIPERs and Prodrug‐Based Approaches

Cell-cycle arrest and senescence in TP53-wild type renal carcinoma by enhancer RNA-P53-bound enhancer regions 2 (p53BER2) in a p53-dependent pathway

(2021) Haibiao Xie et al.   Cell Death & Disease

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

Structure-Based Design of A-1293102, a Potent and Selective BCL-XL Inhibitor

(2021) Zhi-Fu Tao et al.   ACS Medicinal Chemistry Letters

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC).

(2021) Angel Qin et al.   JOURNAL OF CLINICAL ONCOLOGY

Discovery of a Novel BCL-XL PROTAC Degrader with Enhanced BCL-2 Inhibition

(2021) Pratik Pal et al.   JOURNAL OF MEDICINAL CHEMISTRY

E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points

(2021) Aleša Bricelj et al.   Frontiers in Chemistry

NIMBLE: A Phase I/II Study of AZD0466 Monotherapy or in Combination in Patients with Advanced Hematological Malignancies

(2021) Marina Konopleva et al.   BLOOD

Combination Therapy of Bcl-2/X L dual Inhibitor AZD0466 with Acalabrutinib to Overcome Therapeutic Resistance in Aggressive R/R Mantle Cell Lymphoma

(2021) Yijing Li et al.   BLOOD

Amide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity

(2021) Victoria G. Klein et al.   JOURNAL OF MEDICINAL CHEMISTRY

MA02.06 Phase 1b Study of Pelcitoclax (APG-1252) in Combination With Osimertinib in Patients With EGFR TKI-Resistant NSCLC

(2021) L. Zhang et al.   Journal of Thoracic Oncology

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

(2021) Dongwen Lv et al.   Nature Communications

BCL-XL expression is essential for human erythropoiesis and engraftment of hematopoietic stem cells

(2020) Sehar Afreen et al.   Cell Death & Disease

U1 snRNP regulates cancer cell migration and invasion in vitro

(2020) Jung-Min Oh et al.   Nature Communications

PHOTACs enable optical control of protein degradation

(2020) Martin Reynders et al.   Science Advances

Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity

(2020) Estela González‐Gualda et al.   AGING CELL

Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity

(2020) Xuan Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

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

(2020) Hanjie Yi et al.   Cancer Medicine

Development of Mcl-1 inhibitors for cancer therapy

(2020) Arvind Negi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Multi-targeting protein-protein interaction inhibitors: Evolution of macrocyclic ligands with embedded carbohydrates (MECs) to improve selectivity

(2019) Arvind Negi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

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

(2019) Sajid Khan et al.   NATURE MEDICINE

Apoptosis signaling and BCL-2 pathways provide opportunities for novel targeted therapeutic strategies in hematologic malignances

(2018) Huanling Wu et al.   BLOOD REVIEWS

Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation

(2018) Nobumichi Ohoka et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Ligand design for somatostatin receptor isoforms 4 and 5

(2018) Arvind Negi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

N-Alkyl-1,5-dideoxy-1,5-imino-l-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines

(2018) Jian Zhou et al.   BIOORGANIC CHEMISTRY

APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells

(2017) Jing Wang et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

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

(2017) Huogang Wang et al.   Oncotarget

Anacardic Acids from Knema hookeriana as Modulators of Bcl-xL/Bak and Mcl-1/Bid Interactions

(2016) Charlotte Gény et al.   JOURNAL OF NATURAL PRODUCTS

Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon

(2016) Thang Van Nguyen et al.   MOLECULAR CELL

Design, synthesis and preliminary bioactivity studies of 2-thioxo-4-thiazolidinone derivatives as Bcl-2 inhibitors

(2015) Yichao Wan et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Decorated Macrocycles via Ring-Closing Double-Reductive Amination. Identification of an Apoptosis Inducer of Leukemic Cells That at Least Partially Antagonizes a 5-HT2 Receptor

(2015) Jian Zhou et al.   ORGANIC LETTERS

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

From meiogynin A to the synthesis of dual inhibitors of Bcl-xL and Mcl-1 anti-apoptotic proteins

(2014) S. Desrat et al.   CHEMICAL COMMUNICATIONS

338 BM-1252 (APG-1252): a potent dual specific Bcl-2/Bcl-xL inhibitor that achieves complete tumor regression with minimal platelet toxicity

(2014) L. Bai et al.   EUROPEAN JOURNAL OF CANCER

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities

(2014) Carles Galdeano et al.   JOURNAL OF MEDICINAL CHEMISTRY

Endiandric Acid Analogues from Beilschmiedia ferruginea as Dual Inhibitors of Bcl-xL/Bak and Mcl-1/Bid Interactions

(2014) Cécile Apel et al.   JOURNAL OF NATURAL PRODUCTS

Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim

(2014) Chunwei Cheng et al.   Marine Drugs

New Early Eocene Basal tapiromorph from Southern China and Its Phylogenetic Implications

(2014) Bin Bai et al.   PLoS One

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

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

Expedient Synthesis of Highly Potent Antagonists of Inhibitor of Apoptosis Proteins (IAPs) with Unique Selectivity for ML-IAP

(2013) Mitchell Vamos et al.   ACS Chemical Biology

The complex transcriptional landscape of the anucleate human platelet

(2013) Paul F Bray et al.   BMC GENOMICS

Recent Advancements in Small Molecule Inhibitors of Insulin–like Growth Factor-1 Receptor (IGF-1R) Tyrosine Kinase as Anticancer agents

(2013) Arvind Negi et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion

(2013) Neel Sengupta et al.   Molecular Cancer

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

(2013) Andrew J Souers et al.   NATURE MEDICINE

Next Generation Sequencing Analysis of Human Platelet PolyA+ mRNAs and rRNA-Depleted Total RNA

(2013) Antheia Kissopoulou et al.   PLoS One

Inhibitor of Apoptosis (IAP) Proteins-Modulators of Cell Death and Inflammation

(2013) J. Silke et al.   Cold Spring Harbor Perspectives in Biology

Synthesis and biological activities of polyquinoline derivatives: New Bcl-2 family protein modulators

(2012) Emmanuelle Saugues et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Relaxation of the rigid backbone of an oligoamide-foldamer-based α-helix mimetic: identification of potent Bcl-xL inhibitors

(2012) Jeremy L. Yap et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

The dynamics of drug-target interactions: drug-target residence time and its impact on efficacy and safety

(2010) Robert A Copeland   Expert Opinion on Drug Discovery

The BH3 α-Helical Mimic BH3-M6 Disrupts Bcl-XL, Bcl-2, and MCL-1 Protein-Protein Interactions with Bax, Bak, Bad, or Bim and Induces Apoptosis in a Bax- and Bim-dependent Manner

(2010) Aslamuzzaman Kazi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structural Insights into the Design of Small Molecule Inhibitors That Selectively Antagonize Mcl-1

(2010) Paul H. Bernardo et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2008) C. Tse et al.   CANCER RESEARCH