RIPK1 and cancer: We have recently developed non-peptide based hetero-bivalent N-end rule pathway inhibitor called RFC11 (Scheme 1) that shows the ability to restore in vivo stability of various N-end rule substrates leading to various physiological changes.18 Therefore, combination of RFC11, which by inhibiting N-end rule pathway can stabilize RIPK1 with shikonin (already known to elevate expression of RIPK1 in certain cells), is likely to increase drug sensitivity of cancer cells leaving them vulnerable to apoptosis or necroptosis.