Necrostatin-1 - RIPK1 Inhibitor

RIPK1 inhibitor

Necrostatin-1 (Nec-1) is a potent and specific small-molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1, aka RIP1) [1, 2]. RIPK1, through its kinase and scaffolding functions, is a key regulator of apoptosis, necroptosis, and inflammatory pathways.

Learn more on apoptosis and necroptosis

Mode of action:

Necrostatin-1 binds to a hydrophobic pocket of RIPK1, located between the N- and C-terminus of the kinase domain, and locks RIPK1 in an inactive conformation [3]. The Ser/Thr kinase activity of RIPK1 is essential for RIPK1-RIPK3-MLKL necrosome-mediated necroptosis upon TNF-α (tumor necrosis factor-α) signaling [2, 4]. Thus, Nec-1 acts as an inhibitor of RIPK1-mediated necroptosis. The administration of Nec-1 has been shown to reduce cell death and/or mortality in several disease models [4].

Key features:

• Potent and selective inhibitor of RIPK1
• Suppresses RIPK1-dependent necroptosis
• InvitroFit™ grade: each lot is highly pure (≥95%) and functionally tested for necroptosis inhibition

References

1. Degterev A. et al., 2005. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 1: 112-119.
2. Degterev A. et al., 2008. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nature Chemical Biology 4(5), 313-321.
3. Xie T. et al., 2013. Structural Basis of RIP1 Inhibition by Necrostatins. Structure. 21(3):493-499.
4. Speir M. et al., 2021. Targeting RIP kinases in chronic inflammatory disease. Biomolecules. 11:646.