ERG-7 Inhibitors: Targeting the Sterol Biosynthetic Pathway

This invention relates to small molecule anti-fungal compounds, pharmaceutical compositions, and methods of use for the prevention, treatment, or mitigation of fungal diseases in human and veterinary subjects. In particular aspects, the invention provides inhibitors that modulate fungal sterol biosynthesis, including inhibitors of lanosterol synthase (ERG7). These can be used as a sole therapeutic or in combination with standard antifungals to improve efficacy.

Background: 
ERG7 inhibitors target the problem of rising antifungal resistance, particularly to azoles that act later in sterol biosynthesis. Unlike current therapies, such as azoles, echinocandins, polyenes, etc., that suffer from resistance, toxicity, or fungistatic effects, ERG7 inhibitors block an upstream, essential sterol step, causing fungicidal activity and reduced cross-resistance, though achieving fungal selectivity remains a key challenge.

Applications: 

• Small molecule inhibitor
• Antifungal therapeutic
• Combination antifungal therapy
• Human & veterinary fungal prevention, treatment, and mitigation 

Advantages: 

• Selectivity between fungal ERG7 and human lanosterol synthase
• Can be used in combination with standard antifungals
• Addresses resistance to standard antifungals (azole-resistant fungi)
• Attacks fungal cell membrane formation
• Broad medication administration methods
• Reduce fungal related healthcare costs 
• Expand available fungal prevention, treatment, and mitigation medications