NF-56-EJ40 hydrochloride

SKU: orb1819292

Description

NF-56-EJ40 hydrochloride is a highly potent and selective antagonist of the human SUCNR1 (GPR91) receptor, exhibiting an IC50 of 25 nM. It is a valuable research tool for investigating the role of succinate signaling in metabolic and inflammatory diseases in both cellular and animal models.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 2728500-80-7
• MW: 516.46
• Purity: 99.33% (May vary between batches)
• Formula: C₂₇H₃₁Cl₂N₃O₃
• SMILES: O=C(CC1=C(NC(C2=CC=CC(C3=CC=C(CN4CCN(CC4)C)C=C3)=C2)=O)C=CC=C1)O.Cl.Cl
• Target: Succinate Receptor 1 (SUCNR1)
• Solubility: DMSO:5.19 mg/mL (10.05 mM)

Bioactivity

• In Vitro:
  NF-56-EJ40 hydrochloride is bound deep inside the hydrophobic pocket, with the acid group coordinated by the hydroxyl groups of the conserved residues Y832.64 and Y301.39 on one side, and R2817.39 on the other side. The conserved E181.27 is predicted to form an additional hydrogen bond to the piperazine ring of NF-56-EJ40 hydrochloride. E221.31 and N2747.32 in human SUCNR1 are replaced by K181.31 and K2697.32 in rat SUCNR1. These two amino acid exchanges could prevent the binding of NF-56-EJ40 hydrochloride to rat SUCNR1 owing to steric hindrance. Radioligand-binding studies with human SUCNR1 showed partial agreement with our homology model: the Y301.39F mutant of human SUCNR1, shows reduced binding of NF-56-EJ40. Similar effects are observed with the E181.27K and E181.27R mutants, probably owing to steric clashes of the Lys and Arg residues with NF-56-EJ40 hydrochloride and the loss of a hydrogen bond to its piperazine ring. Human SUCNR1 residues are introduced into rat SUCNR1 to form the double mutant K181.31E/K2697.32N (hereafter denoted humanized rat SUCNR1) (Ki of 17.4 nM and 33.5 nM for human and humanized rat SUCNR1, respectively). NF-56-EJ40 hydrochloride increases the thermal stability of both humanized rat SUCNR1 and human SUCNR1, but not that of rat SUCNR1.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

HGPR91, NF-56-EJ40 Hydrochloride, NF56EJ40hydrochloride

Compound Identifiers

PubChem CID

166298600