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iKIX1 is an antifungal agent that can re-sensitize drug-resistant Candida glabrata to azole antifungals. C. glabrata fungal infections that are resistant to azoles are an increasing problem. Drug-resistant C. glabrata most commonly contain point mutations in Pdr1 that render it active. iKIX1 acts by inhibiting the protein–protein interaction between the fungal transcription factor Pdr1 and the KIX domain of the MED15 subunit of the co-activator Mediator, thus inhibiting Pdr1-dependent gene activation of key regulators of the multidrug resistance pathway. iKIX1 reduced efflux pump gene expression and restored azole-sensitivity to PDR1 gain-of-function mutant Candida glabrata strains in plate assays. In mouse assays, combination treatment with iKIX1 and fluconazole showed significant reduction of fungal burden in mice injected with two different azole-resistant C. glabrata strains.
| Molecular Weight | 303.17 |
| Formula | C10H8Cl2N4OS |
| CAS Number | 656222-54-7 |
| Solubility (25°C) | DMSO: 25 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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