GSK2194069

An excellent probe for FASN but, as PK data is missing, it is hard to judge the in vivo dosing. 

GSK2194069 is a potent probe for the beta-ketoacyl reductase domain of hFAS, and has the potential to be useful in exploring the role of fatty acid synthesis in tumour proliferation. Its inhibition of the KS domain is well characterized kinetically and is competitive with the substrate, but not NADPH co-factor. This is verified structurally. In vitro activity is well explored across several cancer cell lines, and is shown to inhibit lipid synthesis at low doses. There is a limited investigation of the selectivity, therefore this compound is more useful as an orthogonal probe as opposed to a high-quality probe in its own right. In vivo investigations were limited to investigation in one organism with one dosing protocol, although tumour volume was shown to decrease more in vivo data such as full PK profile are needed before recommending for in vivo use.