Development of Light-Activated LXR Agonists
Tufan K Mukhopadhyay1, Sabine Willems2, Christopher J Arp1
1Department of Chemistry, New York University, New York City, NY, 10003, USA.
Chemmedchem
|March 10, 2023
Summary
Researchers developed photoswitchable liver X receptor (LXR) agonists for targeted cancer therapy. These compounds activate LXR with light, enhancing chemotherapy efficacy in lung cancer cells while minimizing side effects.
Area of Science:
- Medicinal Chemistry
- Molecular Pharmacology
- Cancer Therapeutics
Background:
- Liver X receptor (LXR) activation is a therapeutic strategy for metabolic diseases and cancer.
- Current LXR agonists cause side effects, limiting their clinical use.
- Photopharmacology offers potential for localized LXR activation to mitigate side effects.
Purpose of the Study:
- To design and develop photoswitchable liver X receptor (LXR) agonists.
- To investigate the potential of these compounds as adjuvant cancer therapy.
- To create a tool for light-dependent LXR activation in cancer cells.
Main Methods:
- Computer-aided drug design based on the T0901317 scaffold.
- Azologization and structure-activity relationship (SAR) evaluation.
- Testing of photoswitchable LXR agonists in human lung cancer cells.
Main Results:
- A novel photoswitchable LXR agonist was developed, active in its (Z)-isomer upon light induction.
- The compound showed low micromolar potency for LXR activation.
- Light-dependent sensitization of human lung cancer cells to chemotherapeutic treatment was observed.
Conclusions:
- Photoswitchable LXR agonists represent a promising strategy for targeted cancer therapy.
- Local activation of LXR via photopharmacology can enhance chemotherapy efficacy.
- This approach may overcome the limitations of systemic LXR agonist administration.
Related Concept Videos
01:25Drug-Receptor Interaction: Agonist
2.6K
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
2.6K
01:11Channel Rhodopsins
2.6K
Most organisms use photoreceptors to sense and respond to light. Examples of photoreceptors include bacteriorhodopsins and bacteriophytochromes in some bacteria, phytochromes in plants, and rhodopsins in the photoreceptor cells of the vertebral retina. The light-sensitive property of these receptors is because of the bound chromophores, such as bilin in the phytochromes and retinal in the rhodopsins.
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...
2.6K
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.2K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
3.2K