I've recently conducted/validated a small molecule screen looking for synergy between an RTK inhibitor and a panel of small molecules. I have two strong hits that appear to be targeting the same thing, but there is no immediate clear mechanism between these two compounds and the RTK. Are there any ideas for identifying the mechanism of synergy without individually analyzing each pathway downstream of the RTK?
Generally, there will be something known about these small molecules or they will be structurally similar to other molecules with known targets. Otherwise, you can probably start at the top of the RTK pathway and work your way down. I guess starting at your phenotype and working your way back up to the RTK is also a good strategy. You also might want to consider some of the antibody arrays that are getting more popular.
What was your synergy measurement? Cell death? Pathway activation?
The hit compounds might not target the RTK pathway, but the likelihood of this is determined by how you have measured synergy.
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