DO264

Reversible Competitive Inhibitor of ABHD12

Structure

Information

  • ABHD12
  • Reversible Competitive Inhibitor
  • up to 1 uM
  • Reviewer recommended concentration: 20-200 nM ideal, up to 1 uM acceptable

In Vitro Validations

Uniprot ID: Q8N2K0
Target Class: Lipid metabolism
Target SubClass: Serine Esterase
Potency: IC50
Potency Value: 11 nM
Potency Assay: Inhibition of lyso-PS hydrolysis
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: yes
Target aliases:
Lysophosphatidylserine lipase ABHD12, C20orf22, AB ...

DOI Reference: 10.1038/s41589-018-0155-8

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:
ABPP studies of DO264 (46) and other representative (thio)urea inhibitors of ABHD12 confirmed excellent selectivity over other serine hydrolases including phosphatidylserine lipases, such PS-PLA1o and ABHD16A and the PLA1-type PI lipase DDHD1.
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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

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

In Cell Rating
In Model Organisms

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 )