RIPK1 inhibitor - Necrostatin-1

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Specific inhibitor of RIPK1 - InvitroFit™

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25 mg

4 x 25 mg


RIPK1 inhibitor

Inhibition of RIPK1-mediated necroptosis using Necrostatin-1
Inhibition of RIPK1-mediated necroptosis using Necrostatin-1

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. 

More details 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



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.


Dose-dependent inhibition of RIPK1 activity
Dose-dependent inhibition of RIPK1 activity

Necrostatin-1 inhibits the TNF-α-induced necroptosis in a dose-dependent manner. THP1-HMGB1-Lucia™ cells were incubated with recombinant human TNF-α (100 ng/ml), Z-VAD-FMK (caspase inhibitor, 25 µM), BV6 (cIAP inhibitor, 5 µM), and increasing concentrations of Necrostatin-1 (RIPK1 inhibitor). After overnight incubation, the level of HMGB1::Lucia released in the supernatant was assessed by measuring the light signal produced using the QUANTI‑Luc™ detection reagent. Data are shown as a percentage (%) cell death induction in absence of RIPK1 inhibitor.

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CAS number: 4311-88-0

Synonym: 5-(1H-Indol-3-ylmethyl)-3-methyl-2-thioxo-4-imidazolidinone

Working concentration range: 0.15 -40 µM for cell culture assays

Solubility: 10 mg/ml (38.6 mM) in DMSO

Formula: C13H13N3OS

Molecular weight: 259.33 g/mol

Quality control:

  • Purity: ≥95% (UHPLC)
  • The inhibitory activity of the product has been validated using in-house cellular assays with THP1-HMGB1-Luciacells.
  • The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.
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Necrostatin-1 is provided as a powder. It is available in two quantities: 

  • inh-ncst1: 25 mg
  • inh-ncst1-4: 4 x 25 mg

 Necrostatin-1 is shipped at room temperature.

 Upon receipt, store at -20°C.

AlertProtect this product from light.

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Chemical structure of Necrostatin-1:

Chemical structure of Necrostatin-1

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