Related Experiment Video
Updated: May 8, 2026
12:19
Photogeneration of N-Heterocyclic Carbenes: Application in Photoinduced Ring-Opening Metathesis Polymerization
Published on: November 29, 2018
BH3 mimetics: status of the field and new developments
1Corresponding Author: Christian Billard, Centre de Recherche des Cordeliers, UMRS 872, Equipe 18, 15 rue de l'Ecole de Médecine, 75006 Paris, France. christian.billard@crc.jussieu.fr.
Molecular Cancer Therapeutics
|August 27, 2013
Summary
BH3 mimetics are novel anticancer agents that trigger apoptosis by targeting BCL-2 family proteins. Recent developments include identifying molecular interactions and characterizing new compounds that selectively inhibit prosurvival proteins.
Area of Science:
- Molecular Biology
- Oncology
- Drug Discovery
Background:
- Targeting apoptosis is a key strategy in cancer therapy.
- BH3-only proteins initiate apoptosis by binding to prosurvival BCL-2 family members.
- BH3 mimetics are small molecules designed to mimic BH3-only proteins, inducing cancer cell death.
Purpose of the Study:
- To review existing BH3 mimetics and their mechanisms.
- To present recent advancements in BH3 mimetic development.
- To highlight novel compounds targeting specific prosurvival proteins.
Main Methods:
- Review of existing literature on BH3 mimetics.
- Analysis of molecular determinants for BH3-protein interactions.
- Characterization of newly developed BH3 mimetic compounds.
Main Results:
- The prototype BH3 mimetic ABT-737 targets BCL-XL, BCL-2, and BCL-W.
- Its derivative ABT-263 shows promise in clinical trials.
- New BH3 mimetics selectively target MCL-1 or BCL-2, or a broader range of proteins.
Conclusions:
- Understanding molecular interactions is crucial for designing effective BH3 mimetics.
- Development of selective BH3 mimetics offers new avenues for cancer treatment.
- These advancements are critical for discovering novel anticancer agents.
Related Concept Videos
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
01:26Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride
Radical substitution reactions can be used to remove functional groups from molecules. The hydrogenolysis of alkyl halides is one such reaction, where the weak Sn–H bond in tributyltin hydride reacts with alkyl halides to form alkanes. Here, the reagent Bu3SnH yields tributyltin halide as a byproduct.
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...
01:25Microbial Interactions: Mutualism
Mutualism is a symbiotic interaction in which all participating organisms benefit. These relationships can be obligate or facultative and are fundamental to ecosystem functions across diverse biological systems.Plant–Fungi MutualismOne well-known example is the association between plant roots and mycorrhizal fungi, such as Rhizophagus species. The fungal hyphae penetrate the root hairs and the epidermis, forming an extensive hyphal network that establishes a symbiotic association. Through this...
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.
02:46Halogenation of Alkenes
Halogenation is the addition of chlorine or bromine across the double bond in an alkene to yield a vicinal dihalide. The reaction occurs in the presence of inert and non-nucleophilic solvents, such as methylene chloride, chloroform, or carbon tetrachloride.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
01:22Bioreactor Controls-III
Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...