Tailored chemical proteomics for covalent inhibitors
Turn your covalent inhibitor into a chemical probe for target engagement and selectivity studies.
Starting from your existing compound, Omivera can help develop a tailored chemical probe that enables you determine where in a biological system and which proteins your inhibitor engages. For a covalent inhibitor, a probe can be built directly from the compound itself by introducing a small bio-orthogonal handle at a position where structure-activity relationship data suggest it will not interfere with binding or reactivity. The warhead, already present in the covalent inhibitor, allows for binding the intended target as well as potential off-targets.
1. Start with your covalent inhibitor
We begin with the compound you want to investigate and assess how it can be adapted for chemical proteomics.
2. Add a click handle
A reporter handle is introduced to create a chemical probe while retaining the relevant properties of the original inhibitor.
3. Study target engagement
The probe can then be used to measure target engagement and compound selectivity in the biological system relevant to your program.
4. Choose the right readout
Depending on the question, studies can use either gel-based profiling or mass-spectrometry-based chemical proteomics.
What questions can this approach answer?
✓ What is the target engagement of the covalent inhibitor?
✓ What is the full set of proteins that your covalent inhibitor reacts with?
Model |
| Project dependent: live cells, cell lysates, or tissues |
Targets |
| Any proteins with a reactive residue that covalently interacts with the inhibitor’s warhead |
Best suited for |
| Target engagement & off-target mapping for covalent inhibitors |