Related Experiment Video
Updated: Aug 7, 2026
06:46
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Selective, orally active MMP inhibitors with an aryl backbone
T E Barta1, D P Becker, L J Bedell
1Pharmacia, Department of Medicinal Chemistry, 4901 Searle Parkway, Skokie, IL 60077, USA. barta@netmug.org
Bioorganic & Medicinal Chemistry Letters
|September 11, 2001
Summary
Researchers explored structure-activity relationships (SAR) and optimized pharmacokinetic (PK) properties in rats for novel aryl hydroxamate sulfonamides. These compounds show activity against matrix metalloproteinase-2 (MMP-2) and MMP-13 while sparing MMP-1.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- Matrix metalloproteinases (MMPs) are implicated in various diseases.
- Selective inhibition of MMPs is a therapeutic goal.
- MMP-1 sparing compounds are desirable to avoid side effects.
Purpose of the Study:
- To describe structure-activity relationship (SAR) exploration.
- To optimize rat pharmacokinetic (PK) properties.
- To identify novel aryl hydroxamate sulfonamides with selective MMP inhibition.
Main Methods:
- Synthesis of novel aryl hydroxamate sulfonamides.
- In vitro assays for MMP activity.
- In vivo pharmacokinetic studies in rats.
- Structure-activity relationship analysis.
Main Results:
- Identification of a series of novel aryl hydroxamate sulfonamides.
- Demonstrated activity against MMP-2 and MMP-13.
- Achieved selectivity by sparing MMP-1 activity.
- Optimized rat PK profiles for lead compounds.
Conclusions:
- Novel aryl hydroxamate sulfonamides demonstrate potent and selective inhibition of MMP-2 and MMP-13.
- These compounds represent promising leads for further drug development.
- The SAR exploration guided the optimization of PK properties for therapeutic potential.
More Related Videos
Related Concept Videos
01:23Role of Matrix Metalloproteases in Degradation of ECM
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
A...
01:29Indirect-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...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
01:24Cholinergic Antagonists: Pharmacokinetics
Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations, while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and the conjunctiva.
01:28Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
01:15Antifungal 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 cholesterol contributes to...