Shuichi Suzuki

Publications (2)3.8 Total impact

• Article: Ago-allosteric modulators of human glucagon-like peptide 2 receptor.

  Kazuto Yamazaki, Hiroki Terauchi, Daisuke Iida, Hironori Fukumoto, Shuichi Suzuki, Takaki Kagaya, Mika Aoki, Koichiro Koyama, Takashi Seiki, Kazuma Takase, Misako Watanabe, Tohru Arai, Kappei Tsukahara, Junichi Nagakawa
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  ABSTRACT: Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-2R), a class-B G protein-coupled receptor (GPCR). Few synthetic agonists have been reported so far for class-B GPCRs. Here, we report the first scaffold compounds of ago-allosteric modulators for human GLP-2R, derived from methyl 2-{[(2Z)-2-(2,5-dichlorothiophen-3-yl)-2-(hydroxyimino)ethyl]sulfanyl}benzoate (compound 1).
  Bioorganic & medicinal chemistry letters 08/2012; 22(19):6126-35. · 2.65 Impact Factor
• Article: Species-specific differences in agonistic activity of ago-allosteric modulators toward glucagon-like peptide 2 receptor.

  Kazuto Yamazaki, Kazuma Takase, Misako Watanabe, Takaki Kagaya, Hiroki Terauchi, Daisuke Iida, Hironori Fukumoto, Shuichi Suzuki, Tohru Arai, Mika Aoki, Takashi Seiki, Kappei Tsukahara, Junichi Nagakawa
  [show abstract] [hide abstract]
  ABSTRACT: Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP- 2R), a class-B G protein-coupled receptor (GPCR) coupled with Gα(s). Few small-molecule agonists had been reported for class-B GPCRs, but we recently reported the first scaffold compounds of ago-allosteric modulators for human GLP-2R. Methyl 2-{[(2Z)-2-(2,5-dichlorothiophen- 3-yl)-2-(hydroxyimino)ethyl]sulfanyl}benzoate (compound 1) and its de-esterified derivative (compound 2) induced placental alkaline phosphatase (PLAP) activity in HEK293 cells overexpressing human GLP-2R and PLAP driven by cAMP response element. In this study, we observed that rat, Syrian hamster, and dog GLP-2Rs also responded to compounds 1 and 2 in the same reporter system. However, no agonistic activity of the compounds toward mouse GLP-2R was detected. Mutagenesis studies showed that mutant human GLP-2Rs with Pro392Leu substitution of mouse GLP-2R for human GLP-2R amino acid residues nullified the PLAP activity of compound 2, although these mutant receptors responded to GLP-2. This finding suggests that the Pro392 residue of human GLP-2R is essential for the agonistic activity of compound 2.
  Biomedical Research 01/2012; 33(6):337-44. · 1.15 Impact Factor