Creative Biolabs has always been devoted to assisting our worldwide clients for developing the next generation of antifungal therapies. Currently, we proudly present our exclusive service to investigate the mechanism of action to support drug discovery process.

Recent antifungal drugs have many side effects which limit their clinical use. For instance, amphotericin B has severe acute and chronic toxicities, and azoles have a low susceptibility to fungal pathogens. To improve drugs' efficiency and reduce their toxicity, understanding particular modes of actions is critical. Although several reviews focused on the mode of action of antifungal compounds and group certain structural with MOA, not all antifungal compounds have known mechanisms of action. Creative Biolabs provides several ways to help our customers determine the mode of actions, which include the following:

Signaling Pathway Analysis

A group of molecules work together via the signal to control one or more cell functions. Drugs can be developed to block these pathways to inhibit or kill fungi. Creative Biolabs provides several techniques, including high content imaging (HCI) and protein interaction mapping (proteomics) to discover the complex gene interactions and pathways.

Target Deconvolution

Target deconvolution terms retrospective identification of the molecular targets that underlie the observed phenotypic responses. It is an important aspect of current drug discovery. Target deconvolution is important for elucidating the mode of action of antifungal drugs and greatly aid structure-activity relationship (SAR) studies and rational drug design. Chemical optimization can be conducted by the configuration of target­specific assays and target­specific side effects, like toxicity can be addressed and reduced. Creative Biolabs provides several techniques for target deconvolution, including affinity chromatography-based methods, expression-cloning-based methods, protein microarrays, reverse-transfected cell microarrays, and biochemical suppression.

Expression Profiling

Creative Biolabs uses various gene expression profiling technologies, like whole genome microarray analysis, to study the molecular mechanisms of antifungal drugs. Expression profiling provides a clearer view of the level of molecular expression of fungi.

We offer several ways of MOA analysis for antifungals, includes:

Interference with Cell Membrane

Given the pivotal role of the plasma membrane in fungal structure and physiological function, therapeutics targeting fungal cell membrane has long been considered as a hotspot. Based on comprehensive knowledge of fungal plasma membrane and unparalleled technique platform, Creative Biolabs has established an integrated service to uncover the MOA of your test compound focusing on the fungal cell membrane.

Interference with Cell Wall

Fungal cell wall represents an ideal target as cell wall is found in all fungal pathogens and being essential for fungal cell viability but not in human cells. The cell wall of fungi plays a crucial role in morphology maintenance, cell rigidity, intracellular homeostasis, ion transport and filtration, antigenic presentation, host interaction, and resistance generation. To better illustrate the antifungal mechanism of action targeting cell wall, Creative Biolabs has built up an integrated platform combining multiple sophisticated assays and high throughput technologies.

Interference with Fungal Protein Synthesis

In the effort to discover novel antifungal compounds by uncovering the MOA of protein synthesis inhibition potential, Creative Biolabs has launched an exclusive technical system, based on profound knowledge of fungi physiology and a comprehensive range of assays. Creative Biolabs conducts a panel of well-designed in vitro assays to elaborate the mechanism of action of potential antifungal compounds, especially in respect of protein synthesis inhibition.

Interference with Fungal Nucleic Acid Synthesis

Although fungal cell envelope has long been considered as the primary target for most antifungal therapies, alternative targets keep emerging during recent years in the effort to overcome fungal infection and drug resistance. Aided by our advanced technique system, scientific staffs in Creative Biolabs conduct multiple delicate tests to facilitate the investigation of the antifungal mechanism of action from custom compounds.

Reference

  1. Carrillo-Muñoz AJ, Giusiano G, Ezkurra PA, et al. (2006) “Antifungal agents: mode of action in yeast cells.” Rev Esp Quimioter 19(2):130-139.

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