Are there any off targets of Necrostatin 1 beyond IDO (and the obvious target, RIP1)?
We have observed prevention of cell death using a compound we study in combination with Nec1 but have used siRNA to demonstrate that RIP1 is not responsible for our compound's induction of cell death.
If I understand you correctly NecI protects cells from your compound-induced cell-death, while siRIP1 do not. Have you tried looking whether RIP1 knockdown cells are dying by apoptosis rather than necrosis??. Could it be difference between lack of RIP1 activity versus lack of RIP1? May be RIP1 knockdown+caspase inhibitor could protect. Just curious!!!
Sorry, I wasn't very clear. Yes, that is correct.
I haven't checked that - that could be something to check! Good idea - thanks!
Also, I did try a RIP3K and a RIP1K inhibitor but it didn't make a difference. I should also try RIp3K inhbitor with siRIP1. thanks!
Hmm - I'll have to pursue it a bit further! Thanks for the response Andreas! I have some ideas as to what might be happening but nothing concrete.
I did find this paper so as you say there are others that observe the same phenomenon: http://www.sciencedirect.com/science/article/pii/S0014579311006302
Hi Robert,
Some off-targets of Nec-1 can be found in Supplementary figure 1 of Christofferson et al., CDDis 2012 (PMID 22695613). Full text is free on PMC.
Best regards,
sasker
There's another paper describing Nec-1 off-target effects: Biton et al., Cell 2011 (KINOME SCAN, supplementary table A1): PAK1 and PKAC-alpha are inhibited >60% by Nec1; MKNK1 is inhibited 59% by Nec1
http://www.sciencedirect.com/science/article/pii/S0092867411001759#mmc1
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