2. Academic Validation
  3. Development of novel neurokinin 3 receptor (NK3R) selective agonists with resistance to proteolytic degradation

Development of novel neurokinin 3 receptor (NK3R) selective agonists with resistance to proteolytic degradation

  • J Med Chem. 2014 Oct 23;57(20):8646-51. doi: 10.1021/jm500771w.
Ryosuke Misu 1,  Shinya Oishi,  Ai Yamada,  Takashi Yamamura,  Fuko Matsuda,  Koki Yamamoto,  Taro Noguchi,  Hiroaki Ohno,  Hiroaki Okamura,  Satoshi Ohkura,  Nobutaka Fujii
Affiliations

Affiliation

  • 1 Graduate School of Pharmaceutical Sciences, Kyoto University , Sakyo-ku, Kyoto 606-8501, Japan.
PMID: 25247671 DOI: 10.1021/jm500771w
Abstract

Neurokinin B (NKB) regulates the release of gonadotropin-releasing hormone (GnRH) via activation of the neurokinin-3 receptor (NK3R). We evaluated the biological stability of NK3R selective agonists to develop novel NK3R agonists to regulate reproductive functions. On the basis of degradation profiles, several peptidomimetic derivatives were designed. The modification of senktide with (E)-alkene dipeptide isostere generated a novel potent NK3R agonist with high stability and prolonged bioactivity.

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