Related Experiment Video

Updated: Mar 27, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
05:17

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Published on: February 9, 2021

2.1K

MmpL3 Inhibitors: Diverse Chemical Scaffolds Inhibit the Same Target

Giovanna Poce1, Sara Consalvi, Mariangela Biava

  • 1Department of Chimica e Tecnologie del Farmaco, Sapienza University of Rome, p.le A. Moro 5, Rome, Italy. giovanna.poce@uniroma1.it.

Mini Reviews in Medicinal Chemistry
|January 19, 2016
PubMed

Insights

Researchers are exploring new drugs targeting MmpL3, a key protein in mycobacteria outer membrane formation. This review focuses on structure-activity relationships for novel anti-tuberculosis agents.

Area of Science:

  • Microbiology
  • Drug Discovery
  • Structural Biology

Background:

  • MmpL3, a member of the Resistance, Nodulation, and Division (RND) superfamily, is crucial for mycobacterial outer membrane formation.
  • MmpL3 facilitates the export of mycolic acids, essential components of the mycobacterial cell envelope.

Purpose of the Study:

  • To review recent advances in the discovery of MmpL3 inhibitors.
  • To highlight structure-activity relationship (SAR) studies for developing novel anti-tuberculosis agents.
  • To provide insights into the mechanisms of action of MmpL3 inhibitors.

Main Methods:

  • Whole-cell based screening of compound libraries.
  • Analysis of structure-activity relationships (SAR) of identified inhibitors.
  • Investigation of inhibitor modes of action.

Main Results:

  • Several diverse chemical scaffolds targeting MmpL3 have been identified against Mycobacterium tuberculosis (Mtb).
  • Some MmpL3 inhibitors show activity against non-mycolic acid-producing pathogens and non-replicating Mtb.
  • Other inhibitors exhibit specific activity against mycobacteria and do not affect non-replicating bacilli.

Conclusions:

  • MmpL3 is a promising target for novel anti-tuberculosis drug development.
  • Understanding SAR is critical for designing potent and specific MmpL3 inhibitors.
  • Further research into MmpL3 inhibitor mechanisms can lead to new therapeutic strategies against TB.

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.6K
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

14.0K

Related Concept Videos

Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
11.2K
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
27
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
17
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
94.8K
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
37
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
1.1K