Fig. 4: Isoxazole 1 is a specific inhibitor of CnAcs1.
From: Discovery and mechanism of a highly selective, antifungal acetyl-CoA synthetase inhibitor
A The activity of isoxazole 1 against purified Saccharomyces cerevisiae Acs1 (ScAcs1), Candida albicans Acs2 (CaAcs2), Aspergillus fumigatus Acs1 (AfAcs1), Coccidioides immitis Acs1 (CiAcs1), and Cryptococcus neoformans Acs1 (CnAcs1). The inhibition curves are representative of three independent experiments showing similar results. B Isoxazole 1 has minimal activity toward human ACSS2. C Single-dose experiment assessing the activity of the human ACSS2 inhibitor MTB-9655 against CnAcs1 at the maximum soluble concentration. Bar indicates the mean of two independent experiments, with the value of the individual replicate shown by dots. D Anti-malarial, PfAcAS inhibitor MMV084978 inhibits CnAcs1 with IC50 = 2.8 µM (R2 = 0.99 for goodness-of-fit by non-linear regression analysis). The IC50 toward PfAcAS is indicated by the arrow. E PfAcAS inhibitor MMV019721 does not inhibit CnAcs1 at the maximum soluble concentration; bar indicates mean with value of individual replicates shown by dots. F Isoxazole 1 minimally inhibits the C. neoformans aceto-acetyl-CoA synthetase CnKbc1 at maximum soluble concentration. Source data are provided as a Source data file.
