Necrostatin-1 Inactive Control (Nec-1i) is a demethylated variant of necrostatin-1, a RIP1 kinase inhibitor.[1] While both Nec-1 and Nec-1i inhibit the immune regulator indoleamine 2,3-dioxygenase, Nec1i is ~ 100-fold less effective than Nec-1 in inhibiting RIP1 kinase in vitro and 10-fold less potent than Nec-1 in a mouse necroptosis assay.[2] However, equally high doses of Nec-1 and Nec-1i are reported to inhibit TNF-induced systemic inflammatory response syndrome in vivo.[2] Nec-1i is often used as an inactive control in studies using Nec-1 to exclude nonspecific off-target effects.
Reference:
[1]. Degterev, A., Hitomi, J., Germscheid, M., et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nature Chemical Biology 4(5), 313-321 (2008).
[2]. Takahashi, N., Duprez, L., Grootjans, S., et al. Necrostatin-1 analogues: Critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 3, e437 (2012).