Terbinafine is an allylamine that works early in the pathway as a non-competitive inhibitor of the enzyme squalene
Squalene epoxidase (SQLE) is a therapeutic target in colorectal cancer (CRC)
The
terbinafine [9] Since squalene epoxidase is on the biosynthetic pathway leading to
Finally, we demonstrated that terbinafine, a SQLE inhibitor, could be repurposed for CRC by synergising with Squalene epoxidase (Erg1p) is inhibited by the allylamine antimycotics, for example terbinafine, and this treatment was shown to induce squalene accumulation (Ryder, 1992; Klobučníková et al
There has only been one clinically confirmed case of terbinafine resistance in dermatophytes, where six sequential Trichophyton rubrum isolates from the same patient were found to be resistant to terbinafine and cross-resistant to other squalene epoxidase (SE) inhibitors
A T1189C mutation was observed in four T
On the basis of functional homologies to p-hydroxybenzoate hydroxylase (PHBH) from Pseudomonas fluorescens, the Erg1 protein contains two flavin adenine dinucleotide (FAD) domains and one nucleotide
This study documented a step in the global spread of resistance
Squalene epoxidase (also called squalene monooxygenase) catalyses the conversion of squalene into 2,3-oxidosqualene by epoxidation and is regarded as the rate-limiting enzyme for sterol and saponin biosynthesis
Key message We cloned two squalene epoxidases and five oxidosqualene cyclases, and identified their function using CRISPR/Cas9 tool and yeast heterologous expression
(A) Terbinafine, a Food and Drug Administration-approved drug targeting SQLE, dose-dependently suppressed cell viability of HT29 and DLD1 cells, and primary CRC organoids
What is the usual dose regime for terbinafine? Topical terbinafine is applied to the affected area once or twice daily for one to four weeks
Results
It has activity against most dermatophytes, and it has approval for use as an oral therapy for the treatment of onychomycosis
Physicians should be aware of the risk factors for resistance development, and engage in antifungal stewardship practices such as directed diagnosis and treatment of dermatophytosis and Squalene Epoxidase Induces Nonalcoholic Steatohepatitis Via Binding to Carbonic Anhydrase III and is a Therapeutic Target was identified using co-immunoprecipitation and Western Blot
In constrast, inhibition of rat liver squalene epoxidase only occurs at higher drug concentrations (K i =77 μ m), and is competitive with squalene
After this, the binding competence of the However, large-scale cultivation of S