Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury

I have no idea on this one, that's what your genius doctor is for.
http://www.nature.com/nchembio/journal/v9/n3/full/nchembio0313-192a.html
In this Article¹, we described a small-molecule inhibitor of necroptosis, termed Necrostatin-1 (Nec-1). Since the original publication, additional data regarding the properties of Nec-1 have been reported, including off-target activity and metabolic stability in mice, that are important in designing in vitro and, especially, in vivo experiments with Nec-1.
Teng et al.² reported an optimized derivative of Nec-1, termed 7-Cl-O-Nec-1 (66 in ref. 2), that was used in ref. 1 to demonstrate the protection in an ischemic brain injury model. This molecule showed higher activity in inhibiting necroptosis in Jurkat cells than Nec-1 (EC₅₀ = 210 nM versus EC₅₀ = 490 nM), no nonspecific cytotoxicity at high concentrations (~100 mM) and reasonable pharmacokinetic characteristics following intravenous administration in mice. Degterev et al.³ subsequently reported that Nec-1 shows limited metabolic stability, which is substantially improved with 7-Cl-O-Nec-1. Takahashi et al.⁴ also reported that Nec-1 showed paradoxical toxicity at lower, but not higher, doses in a mouse model of systemic inflammatory stress syndrome (SIRS). No such toxicity was observed with 7-Cl-O-Nec-1. Thus, for in-cell and in vivo experiments, we recommend the use of 7-Cl-O-Nec-1.
Muller et al.⁵ reported that Nec-1, also known by its chemical name of methylthiohydantoin-tryptophan, is a micromolar inhibitor of indolamine 2,3-deoxygenase (IDO) with EC₅₀ = 11.4 mM in a cell-based assay. Thus, given the ~20-fold higher activity of Nec-1 in a necroptotic assay, the use of lower concentrations of this molecule could be helpful in distinguishing between inhibition of necroptosis and IDO-related processes. Another known inhibitor of IDO, 1-methyl-DL-tryptophan, lacks activity against necroptosis as reported by both Degterev et al.³ and Takahashi et al.⁴ Notably, both reports show that optimized 7-Cl-O-Nec-1 lacks activity against IDO. Overall, potential nonspecific toxicity, inhibition of IDO and limited stability of Nec-1 should be taken into account when the molecule is used in vivo, whereas 7-Cl-O-Nec-1 lacks these liabilities and thus represents a superior choice for in vivo studies.