Nec-1s

• CAT Number: I005116
• CAS Number: 852391-15-2
• Molecular Formula: C₁₃H₁₂ClN₃O₂
• Molecular Weight: 277.71
• Purity: ≥95%
• Synonyms: Necrostatin 1s; Nec-1s; 5-[(7-Chloro-1H-indol-3-yl)methyl]-3-methyl-2,4-imidazolidinedione
• Target: TNF-α
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 50 nM (EC50)
• IUPAC Name: 5-[(7-chloro-1H-indol-3-yl)methyl]-3-methylimidazolidine-2,4-dione
• InChI: InChI=1S/C13H12ClN3O2/c1-17-12(18)10(16-13(17)19)5-7-6-15-11-8(7)3-2-4-9(11)14/h2-4,6,10,15H,5H2,1H3,(H,16,19)
• InChIKey: WIKGAEMMNQTUGL-UHFFFAOYSA-N
• SMILES: CN1C(=O)C(NC1=O)CC2=CNC3=C2C=CC=C3Cl

Nec-1s (CAT: I005116) is a potent and selective inhibitor of necroptosis, a regulated form of cell death that plays a role in various pathological conditions. Nec-1s precisely target and inhibits receptor-interacting protein kinase 1 (RIPK1), a key regulator of necroptosis signaling. By blocking RIPK1 activity, Nec-1s prevent the formation of the necrosome complex and subsequent cell death. This compound has demonstrated efficacy in several disease models associated with necroptosis, including neurodegenerative disorders, ischemic injury, and inflammatory diseases. Nec-1s represents a valuable tool for studying the molecular mechanisms of necroptosis and has potential therapeutic applications in conditions where necroptosis contributes to tissue damage.

Reference

1. Sci Rep. 2017 Feb 10;7:42159. doi: 10.1038/srep42159.
Inhibition of Receptor-Interacting Protein Kinase 1 with Necrostatin-1s ameliorates disease progression in elastase-induced mouse abdominal aortic aneurysm model.
Wang Q(1), Zhou T(1), Liu Z(1)(2), Ren J(1), Phan N(1), Gupta K(1), Stewart DM(1), Morgan S(1), Assa C(1), Kent KC(1), Liu B(1).
Author information:
(1)Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA. (2)Department of Vascular Surgery, 2nd Affiliated Hospital School of Medicine, Zhejiang University, Zhejiang, China.
Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s). Seven days after aneurysm induction by elastase perfusion, mice were randomly administered DMSO, Nec-1 (3.2 mg/kg/day) and Nec-1s (1.6 mg/kg/day) via intraperitoneal injection. Upon sacrifice on day 14 postaneurysm induction, the aortic expansion in the Nec-1s group (64.12 ± 4.80%) was significantly smaller than that of the DMSO group (172.80 ± 13.68%) (P < 0.05). The mean aortic diameter of Nec-1 treated mice appeared to be smaller (121.60 ± 10.40%) than the DMSO group, though the difference was not statistically significant (P = 0.1). Histologically, the aortic structure of Nec-1s-treated mice appeared normal, with continuous and organized elastin laminae and abundant αActin-expressing SMCs. Moreover, Nect-1s treatment diminished macrophage infiltration and MMP9 accumulation and increased aortic levels of tropoelastin and lysyl oxidase. Together, our data suggest that pharmacological inhibition of necroptosis with Nec-1s stabilizes pre-existing aneurysms by diminishing inflammation and promoting connective tissue repair.