U18666A

More data is needed for this compound to judge it as a probe. No panel data is provided neither within target family nor outside. Crosslinking experiments have identified the proposed target. Analogues and some crude SAR are reported in the paper. Less active analogues were used as controls. Lacking data to be able to judge in vivo dosing. The compound seems to have been in vivo as a Seladin-1 inhibitor 24-dehydrocholesterol reductase https://doi.org/10.1159/000488765:  Moreover it also  inhibits  the microsomal antiestrogen binding site of AEBS a hetero-oligomeric complex, composed of 3β-hydroxysterol-Δ8-Δ7-isomerase (D8D7I) and 3β-hydroxysterol-Δ7-reductase (DHCR7) with a  Ki =84 nM and  cholesterol-5,6-epoxide hydrolase ChEH  with a Ki= 90 nM  DOI: 10.1073/pnas.1002922107

With very little characterization, it is difficult to judge the quality of this compound. There is no selectivity screening and only a single on-target cellular assay. The data has not been validated using an orthogonal assay format. The animal data is also sparse and lacks PK values that would be informative related to its use.

U18666A is a chemical probe for NPC1 that transports cholesterol from the lysosomal membrane. In cells U18666A inhibits cholesterol transesterification and SREBP2 processing at nM concentrations. U18666A has been shown to bind its target NPC1 by using a benzophenone derivative of U18666A that was crosslinked to NPC1. The target protein NPC1 is important in cholesterol homeostasis maintenance and Ebola virus infection, however, the U18666A binding site does not seem to be required for virus entry.
In vivo studies need further fine tuning of dosing and delivery route. Literature suggests:  Feline peritonitis virus in vivo exposure 2.5mg/kg (31963705), ebola virus pathogenesis 2mg/kg in vivo (26015498), prion propagation in vivo 10mg/kg (17409533). Pharmacokinetic and pharmacodynamic studies would be beneficial.