JNJ-28583113

• CAT Number: I041192
• CAS Number: 2765255-93-2
• Molecular Formula: C19H21F3N2O2
• Molecular Weight: 366.38
• Purity: ≥95%
• Synonyms: ethyl 2-[3-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol-1-yl]acetate
• InChI: InChI=1S/C19H21F3N2O2/c1-2-26-17(25)12-24-16-7-5-3-4-6-15(16)18(23-24)13-8-10-14(11-9-13)19(20,21)22/h8-11H,2-7,12H2,1H3
• InChIKey: WOERTJPEDOUEDS-UHFFFAOYSA-N
• SMILES: CCOC(=O)CN1C2=C(CCCCC2)C(=N1)C3=CC=C(C=C3)C(F)(F)F

JNJ-28583113 is an TRPM2 antagonist with brain permeability. JNJ-28583113 inhibits TRPM2 blocked phosphorylation of GSK3α and β subunits. JNJ-28583113 protects cells from oxidative stress induced cell death. JNJ-28583113 also suppresses cytokine release in response to pro-inflammatory stimuli in microglia[1].
JNJ-28583113 inhibits TRPM2 in cells overexpressing chimpanzee (IC50=100 nM), rat (IC50=25 nM), and human (IC50=126 nM), respectively[1].
JNJ-28583113 (3 nM, 30 nM, and 1 μM; 200 s) exhibits electrophysical characterization in ADPR-induced currents recorded in hTRPM2-HEK-inducible cells[1].
JNJ-28583113 (10 μM; 1 h) prevents cells from H2O2 induced cell death up to 1 mM of H2O2. JNJ-28583113 (10 μM; 1 h) also protects HeLa cells from H2O2 (10 μM; 1 h) induced morphological changes[1].
JNJ-28583113 (10 mg/kg, 2 ml/kg; sc; single dose) is brain penetrant, and achieves 400 ng/mL in the brain compartment[1].

Reference

[1]. Fourgeaud L, et al. Pharmacology of JNJ-28583113: A novel TRPM2 antagonist. Eur J Pharmacol. 2019 Jun 15;853:299-307.
 [Content Brief]