Necrosulfonamide

Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways[1][2][3][4][5][6][7].

Product Specifications

CAS Number

[1360614-48-7]

UNSPSC

12352005

Hazard Statement

H302, H315, H319, H335

Target

Caspase; Heme Oxygenase (HO) ; Interleukin Related; Keap1-Nrf2; Mixed Lineage Kinase; Necroptosis; NO Synthase; NOD-like Receptor (NLR) ; Pyroptosis; TNF Receptor

Type

Reference compound

Related Pathways

Apoptosis; Immunology/Inflammation; MAPK/ERK Pathway; Metabolic Enzyme/Protease; NF-κB

Applications

Cancer-Kinase/protease

Field of Research

Endocrinology; Metabolic Disease; Inflammation/Immunology; Neurological Disease; Cardiovascular Disease

Assay Protocol

https://www.medchemexpress.com/Necrosulfonamide.html

Concentration

10mM

Purity

99.47

Solubility

DMSO : ≥ 28 mg/mL

Smiles

O=C(NC1=CC=C(S(=O)(NC2=NC=CN=C2OC)=O)C=C1)/C=C/C3=CC=C([N+]([O-])=O)S3

Molecular Formula

C18H15N5O6S2

Molecular Weight

461.47

Precautions

H302, H315, H319, H335

References & Citations

[1]Sun L, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148 (1-2) :213-227.|[2]Yang W, et al. Necrosulfonamide ameliorates intestinal inflammation via inhibiting GSDMD-medicated pyroptosis and MLKL-mediated necroptosis. Biochem Pharmacol. 2022 Dec;206:115338.|[3]Zhou XY, et al. The brain protection of MLKL inhibitor necrosulfonamide against focal ischemia/reperfusion injury associating with blocking the nucleus and nuclear envelope translocation of MLKL and RIP3K. Front Pharmacol. 2023 Oct 24;14:1157054. |[4]Zhang J, Wei K. Necrosulfonamide reverses pyroptosis-induced inhibition of proliferation and differentiation of osteoblasts through the NLRP3/caspase-1/GSDMD pathway. Exp Cell Res. 2021 Aug 15;405 (2) :112648. |[5]Liu Y, et al. Necrosulfonamide promotes hair growth and ameliorates DHT-induced hair growth inhibition. J Dermatol Sci. 2024 Aug;115 (2) :64-74.|[6]Wu YL, et al. Gasdermin D Inhibitor Necrosulfonamide Alleviates Lipopolysaccharide/D-galactosamine-induced Acute Liver Failure in Mice. J Clin Transl Hepatol. 2022 Dec 28;10 (6) :1148-1154. |[7]Kim DY, Leem YH, Kim HS. MLKL Inhibitor Reduces Oxidative Stress, Inflammation, and Dopaminergic Neuronal Cell Death in MPTP-Induced Parkinson's Disease Mouse Model. Biomol Ther (Seoul) . 2025 May 1;33 (3) :429-437.