DO264
Reversible Competitive Inhibitor of ABHD12
Structure
In Cells
In Model Organisms
Probe DO264 is in the process of SERP review.
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SERP ratings and comments
SERP Ratings
SERP Comments:
DO264 is a high quality probe for reversible inhibition of human and mouse lyso-PS lipase ABHD12. The probe is effective and has excellent selectivity in cell lysates, in cell culture models, and can be used in in vivo experiments to block ABHD12 activity in the mouse brain. Gel-based competitive ABPP analysis indicates that DO264 also engages with ABHD12 in liver, spleen and lung tissues. Use of an activity-based probe with quantitative mass spectrometry and competitive in-gel analyses demonstrate excellent selectivity among endogenous serine hydrolases when used at the recommended concentrations. An inactive control analog (S)-DO271 provides a selectivity control.
(last updated: 13 Aug 2020 )
SERP Ratings
SERP Comments:
This probe is of reasonable high quality, but there are two concerns, based on the lack of available data (as opposed to existing negative data). 1) How selective is the probe outside of the serine hydrolase family? The data reported is using the FP probe, which only allows in-family comparisons. 2) What is the PK of the compound, when dosed IP and PO? With unknown broad selectivity and unknown exposure, there is some concern that in vivo data will be misinterpreted.
(last updated: 5 Sept 2020 )