885434-70-8

Basic information

• Product Name: HJC-0350
• Synonyms: HJC 0350;HJC0350;HJC-0350;1-(Mesitylsulfonyl)-2,4-diMethyl-1H-pyrrole;2,4-dimethyl-1-[(2,4,6-trimethylphenyl)sulfonyl]-1H-pyrrole;2,4-Dimethyl-1-[(2,4,6-trimethylphenyl)sulfonyl]-1H-pyrrole HJC 0350
• CAS NO: 885434-70-8
• Molecular Formula: C₁₅H₁₉NO₂S
• Molecular Weight: 277.38186
• Product Categories: Inhibitors
• Mol File: 885434-70-8.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 434.6±55.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.13±0.1 g/cm3(Predicted)
• Storage Temp.: room temp
• Solubility: DMSO: soluble5mg/mL, clear
• PKA: -6.94±0.70(Predicted)
• CAS DataBase Reference: HJC-0350(CAS DataBase Reference)
• NIST Chemistry Reference: HJC-0350(885434-70-8)
• EPA Substance Registry System: HJC-0350(885434-70-8)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 885434-70-8(Hazardous Substances Data)

Usage

Uses

HJC 0350 is a potent and selective inhibitor of EPAC2 and exhibits no inhibition of EPAC1.

Biological Activity

hjc 0350 is a potent and selective antagonist of epac2 with ic50 value of 0.3 μm [1].camp/camp regulated guanine nucleotide exchange factor (epac/camp-gef) is a guanine nucleotide exchange factor for the small gtpases rap1 and rap2 in response to intracellular camp. epac2 is mainly expressed in the central nervous system, pancreas and adrenal gland [1].hjc 0350 is a potent and selective epac2 antagonist. hjc 0350 competed with 8-nbd-camp in binding recombinant fusion protein epac2 with ic50 value of 0.3 μm and exhibited 133-fold more potent than camp, which competed with 8-nbd-camp in binding epac2 with ic50 value of 40 μm. in the presence of 25 μm camp, hjc 0350 (25 μm) inhibited epac2 gef activity but had no effect on epac1-mediated rap1-gdp exchange activity and camp-mediated pka activation, which suggested that hjc 0350 was epac2-specific antagonist. in hek293 cells expressing epac1- or epac2-based fluorescence resonance energy transfer (fret) sensor (epac2-fl or epac1-fl), hjc 0350 (10 μm) completely inhibited the 007-am (a membrane permeable epac selective camp analogue) induced decrease of fret in hek293/epac2-fl cells but had no effect on hek293/epac1-fl cells [1].

references

[1]. chen h, tsalkova t, chepurny og, et al. identification and characterization of small molecules as potent and specific epac2 antagonists. j med chem, 2013, 56(3): 952-962.

Upstream product

• 625-82-1 2,4-dimethyl-1H-pyrrole 
• 773-64-8 2-mesitylenesulphonyl chloride 

Relevant articles and documents

Identification and characterization of small molecules as potent and specific EPAC2 antagonists

EPAC1 and EPAC2, two isoforms of exchange proteins directly activated by cAMP (EPAC), respond to the second messenger cAMP and regulate a wide variety of intracellular processes under physiological and pathophysiological circumstances. Herein, we report the chemical design, synthesis, and pharmacological characterization of three different scaffolds (diarylsulfones, N,N-diarylamines, and arylsulfonamides) as highly potent and selective antagonists of EPAC2. Several selective EPAC2 antagonists have been identified including 20i (HJC0350), which has an apparent IC50 of 0.3 μM for competing with 8-NBD-cAMP binding of EPAC2 and is about 133-fold more potent than cAMP. Compounds 1 (ESI-05), 14c (HJC0338), and 20i, selected from each series, have exhibited no inhibition of EPAC1-mediated Rap1-GDP exchange activity at 25 μM, indicating that they are EPAC2-specific antagonists. Moreover, live-cell imaging studies using EPAC1, EPAC2, or PKA FRET sensor also demonstrate that 20i functions as an EPAC2 specific antagonist.