HJC-0350 Chemical Properties

Boiling point:

434.6±55.0 °C(Predicted)

Density 

1.13±0.1 g/cm3(Predicted)

storage temp. 

room temp

solubility 

DMSO: soluble5mg/mL, clear

pka

-6.94±0.70(Predicted)

form 

powder

color 

white to beige

Safety Information

WGK Germany 

3

HJC-0350 Usage And Synthesis

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].

Synthesis

To a 5 mL solution of 2,4-dimethyl-1H-pyrrole (24 mg, 0.25 mmol) and 2,4,6-trimethylbenzenesulfonyl chloride (218 mg, 1.0 mmol) in tetrahydrofuran (THF) was slowly added 60% sodium hydride (NaH, 40 mg, 1.0 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction solution was diluted with ethyl acetate (EtOAc, 50 mL) and washed sequentially with 1N hydrochloric acid (HCl, aq., 10 mL) and saturated saline (10 mL). The organic layer was dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=10/1) to afford the target compound 2,4-dimethyl-1-((2,4,6-trimethylphenyl)sulfonyl)-1H-pyrrole as a light red solid (40 mg, 58% yield).1H NMR (600 MHz, CDCl3) δ 7.01 (s, 1H), 6.95 (s 2H), 5.77 (s, 1H), 2.49 (s, 6H), 2.31 (s, 3H), 2.00 (s, 3H), 1.99 (s, 3H).13C NMR (150 MHz, CDCl3) δ 143.8, 140.2, 133.8, 132.2, 130.2, 119.7, 119.2, 114.5, 23.4, 21.1, 114.5, 13.4, 21.1, 114.5, 114.5 23.4, 21.1, 12.6, 11.8.

storage

Store at +4°C

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.

HJC-0350(885434-70-8)Related Product Information

• PD 0325901
• RO-31-8220
• AS-252424
• CEP-18770
• Gentamicin sulfate
• PRT062607 (Hydrochloride)