Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

X-ray Crystallography-Guided Design and Synthesis of Cyclopentyl Heteroaryl Carboxylic Acid-Based Inhibitors of the SARS-CoV-2 Nsp3 Macrodomain (Mac1).

Journal of medicinal chemistry·2026
Same author

Structure-Guided Optimization of Novel Inhibitors of <i>Plasmodium</i> Lysyl-tRNA Synthetase with Multistage Activity against Malaria Parasites.

Journal of medicinal chemistry·2026
Same author

A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader.

Nature communications·2026
Same author

Discovery of AZD9750, an Orally Bioavailable Androgen Receptor Degrader for the Treatment of Prostate Cancer.

Journal of medicinal chemistry·2026
Same author

Discovery and Characterization of GLPG3808, a PAPD5/7 Inhibitor for Suppression of Hepatitis B Viral Infections.

Journal of medicinal chemistry·2026
Same author

HBsAg Suppression by a New Series of HBV RNA Destabilizers: Discovery and Effects on In Vitro Neurite Outgrowth.

Journal of medicinal chemistry·2026

Related Experiment Video

Updated: Jan 8, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

10.9K

Optimization and Chemoproteomic Profiling of a Selective, Covalent Bfl-1-Targeting Cellular Tool.

J Henry Blackwell1, Simon C C Lucas2, Giovanni Battocchio3

  • 1Chemistry and DMPK, Oncology Targeted Discovery, AstraZeneca, Cambridge CB2 0AA, U.K.

Journal of Medicinal Chemistry
|December 23, 2025
PubMed
Summary

Researchers discovered a potent chemical probe that selectively labels Bfl-1 (Bcl-2-associated factor B), a protein in the Bcl-2 family. This probe shows high selectivity and effectiveness in cellular assays and animal studies.

More Related Videos

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
14:02

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

9.0K
FIBS-enabled Noninvasive Metabolic Profiling
09:16

FIBS-enabled Noninvasive Metabolic Profiling

Published on: February 3, 2014

10.3K

Related Experiment Videos

Last Updated: Jan 8, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

10.9K
Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
14:02

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

9.0K
FIBS-enabled Noninvasive Metabolic Profiling
09:16

FIBS-enabled Noninvasive Metabolic Profiling

Published on: February 3, 2014

10.3K

Area of Science:

  • Chemical Biology
  • Molecular Biology
  • Drug Discovery

Background:

  • Bcl-2 family proteins regulate apoptosis.
  • Bfl-1 is an antiapoptotic member of the Bcl-2 family.
  • Targeting Bfl-1 is a strategy for cancer therapy.

Purpose of the Study:

  • To discover and optimize a potent and irreversible cellular probe for selective Bfl-1 labeling.
  • To assess the selectivity and cellular potency of novel Bfl-1 inhibitors.
  • To evaluate the in vivo pharmacokinetics and off-target interactions of Bfl-1 probes.

Main Methods:

  • Synthesis and optimization of a chemical series targeting Bfl-1.
  • Cellular assays to determine potency and caspase activation.
  • In vivo pharmacokinetic studies.
  • Chemoproteomic analyses for proteome-wide selectivity profiling.

Main Results:

  • A potent and irreversible cellular probe for Bfl-1 was discovered and optimized.
  • Compound 25 demonstrated high selectivity for Bfl-1 over related proteins (k_inact/K_I = 9300 M^-1s^-1).
  • Submicromolar concentrations of compound 25 elicited caspase activation in cellular assays.
  • Chemoproteomic analysis provided insights into off-target interactions.

Conclusions:

  • The developed chemical probe offers selective and potent inhibition of Bfl-1.
  • The probe exhibits favorable cellular activity and pharmacokinetic properties.
  • Chemoproteomic profiling is crucial for understanding selectivity and guiding further optimization of Bfl-1 inhibitors.