As a pioneer company in the field of drug discovery, Creative Biolabs is committed to promoting the development of drug discovery for numerous diseases. Based on years of experience and advanced technology, we are able to provide a full range of antifungal drug discovery services against multiple targets. Now we are happy to introduce our antifungal drug discovery service against HSP90 and HSP90-dependent signaling.
Introduction of HSP90 and HSP90-dependent Signaling
The heat shock protein 90 (Hsp90) is a molecular chaperone belonging to the highly conserved family of heat shock proteins (Hsps), which rapidly accumulate in the cytosol in response to heat and environmental challenges such as antifungal drugs, oxidative stress, and heavy metal exposure among others. It is highly abundant in cells even in a non-stressful state and increases further in response to different forms of stress. Studies have shown that Hsp90 can associate with several proteins involved in signaling, metabolism, cell growth, transcription, protein trafficking, chromatin remodeling, and stress response, among others. As an ATP-dependent molecular chaperone, Hsp90 could interact with multiple proteins involved in adaptation to stress and high temperatures. By modulating protein stability, Hsp90 can alter the ratio of active to inactive protein, thus adding an additional layer of regulation to signal transduction cascades.
Fig.1 The role of Hsp90 in fungal drug resistance. (Cowen, 2018)
HSP90 and HSP90-dependent Signaling as Potential Antifungal Target
It has been reported that Hsp90 has the ability to regulate complex cellular circuitry in eukaryotes by stabilizing regulators of cellular signaling. In fungi, Hsp90 acts as a biological transistor regulating the activity of fungal signaling networks and has been demonstrated to mediate drug (such as azole) resistance and biofilm formation in diverse fungal species. As a consequence, inhibiting Hsp90 disrupts a plethora of cellular processes and has broad therapeutic potential against diverse eukaryotic pathogens including the protozoan parasites Plasmodium falciparum and Trypanosoma evansi as well as numerous fungal species. What’s more, inhibiting Hsp90 can enhance the activity of existing antifungals, rendering resistant pathogens more responsive to treatment, and can also block the emergence of drug resistance, creating fungicidal drug combinations.
During the past years, Creative Biolabs has successfully established a state-of-the-art technology platform for antifungal drug discovery. We are able to provide high-quality target identification and validation service using numerous approaches, such as WGS, computer-aided target identification and validation, gene expression profiling, etc. In addition to HSP90 and HSP90-dependent signaling, we are confident in exploiting other potential cellular function-related targets for antifungal drug discovery, which including but not limited to:
Targeting Hsp90 in fungal pathogens has been used as a powerful therapeutic strategy which may provide an even broader therapeutic paradigm for infectious diseases. Our professional scientists will do their best to promote the development of your programs. For more detailed information, please feel free to contact us.
Reference
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