Description
Key facts
CAS number:432531-71-0,
Purity:>98%,
Form:SolidSee storage information,
Molecular weight:461.5 Da,
Molecular formula:C18H15N5O6S2,
PubChem:1566236,
Nature:Synthetic,
Solubility:Soluble in DMSO to 25 mM,
Biochemical name:Necrosulfonamide,
Biological description:Potent, selective necroptosis inhibitor (IC50 = 0.2 μM). MLKL blocker. Selectively blocks necrosis downstream of RIP3 activation. Shows selective antinecrotic effects.,
Canonical smiles:COC1=NC=CN=C1NS(=O)(=O)C2=CC=C(C=C2)NC(=O)C=CC3=CC=C(S3)[N+](=O)[O-],
Isomeric smiles:COC1=NC=CN=C1NS(=O)(=O)C2=CC=C(C=C2)NC(=O)/C=C/C3=CC=C(S3)[N+](=O)[O-],
InChi:InChI=1S/C18H15N5O6S2/c1-29-18-17(19-10-11-20-18)22-31(27,28)14-6-2-12(3-7-14)21-15(24)8-4-13-5-9-16(30-13)23(25)26/h2-11H,1H3,(H,19,22)(H,21,24)/b8-4+,
InChiKey:FNPPHVLYVGMZMZ-XBXARRHUSA-N,
IUPAC Name:(E)-N-[4-[(3-methoxypyrazin-2-yl)sulfamoyl]phenyl]-3-(5-nitrothiophen-2-yl)prop-2-enamide
Properties and Storage Information:
Shipped at conditions-Ambient - Can Ship with Ice, Appropriate short-term storage conditions--20°C, Appropriate long-term storage conditions--20°C, Storage information-It is important to note that this product is reported to be light sensitive, Store in the dark, Store under desiccating conditions
Supplementary Information:
This supplementary information is collated from multiple sources and compiled automatically.
MLKL also known as mixed lineage kinase domain-like protein plays a critical role in the process of necroptosis a form of programmed cell death. The MLKL protein has a molecular weight of approximately 54 kDa. The protein exists mainly within the cytoplasm but translocates to the plasma membrane during cell death execution. Expression of MLKL happens in various tissues indicating its wide biological importance. Phosphorylation of MLKL often referred to as p-MLKL is key to triggering its activity marking the transition from an inactive to an active state during necroptosis.
Biological function summary
The MLKL protein acts as an executioner of cell death by forming a complex that disrupts the plasma membrane integrity. This process is downstream of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) which phosphorylates MLKL to form the active necrosome complex. Active MLKL oligomerizes and migrates towards the inner leaflet of the plasma membrane binding to phosphatidylinositol phosphates which assists in pore formation and cellular rupture. The ability to measure MLKL activity levels such as via MLKL ELISA kits is important for understanding necrotic processes in detailed studies.
Pathways
MLKL is integrally involved in the necroptotic pathway alongside RIPK1 and RIPK3 which are key initiators of necroptosis. Phosphorylated MLKL acts downstream of RIPK3 resulting in cell death without caspase activation distinguishing necroptosis from apoptosis. MLKL and RIPK3 are tightly linked within this pathway with MLKL phosphorylation serving as a vital event for the execution phase. The necroptosis pathway is part of larger networks including inflammatory response pathways highlighting the importance of MLKL's role beyond sheer cell death.
MLKL has been implicated in various inflammatory conditions and neurodegenerative diseases. The dysregulation of necroptosis can contribute to disorders such as inflammatory bowel disease and amyotrophic lateral sclerosis. In inflammatory bowel disease increased levels of p-MLKL might lead to excessive cell death exacerbating inflammation. Similarly in neurodegenerative disorders the harmful activation of MLKL may accelerate neuronal cell death. Key interactions with proteins like RIPK3 and RIPK1 highlight MLKL's involvement in these pathological processes making it a potential target for therapeutic intervention.
