2. Academic Validation
  3. Discovery of DS-1150b, a novel xanthene compound for activating GLUT4 translocation

Discovery of DS-1150b, a novel xanthene compound for activating GLUT4 translocation

  • Bioorg Med Chem Lett. 2025 Jul 1:122:130191. doi: 10.1016/j.bmcl.2025.130191.
Masaki Meguro 1,  Fuminao Doi 2,  Tsuyoshi Soneda 3,  Shinji Furuzono 2,  Masahiro Konishi 4,  Jun Harada 2,  Jun Tanaka 2,  Shinichi Inoue 5,  Makoto Ono 6,  Katsuji Kagechika 2
Affiliations

Affiliations

  • 1 Shinagawa R&D Center, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: meguro.masaki.i2@daiichisankyo.co.jp.
  • 2 Shinagawa R&D Center, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 3 Process Technology Research Laboratories, Technology Division, Daiichi Sankyo Co., Ltd., 1-12-1 Shinomiya, Hiratsuka-shi, Kanagawa 254-0014, Japan.
  • 4 DS Corporate Strategy Department, Daiichi Sankyo Co., Ltd., 3-5-1 Nihonbashi-Honcho, Chuo-ku, Tokyo 103-8426, Japan.
  • 5 Daiichi Sankyo Inc., 211 Mt. Airy Road, Basking Ridge, NJ 07920, USA.
  • 6 Quality Assurance Department, Daiichi Sankyo Co., Ltd., 3-5-1 Nihonbashi-Honcho, Chuo-ku, Tokyo 103-8426, Japan.
PMID: 40122472 DOI: 10.1016/j.bmcl.2025.130191
Abstract

The glucose transporter 4 (GLUT4) is a high-affinity glucose transporter that is predominantly expressed in the skeletal muscle, myocardium, and adipose tissue, and is the rate-limiting transporter of insulin-stimulated glucose uptake. Compounds that enhance the process of GLUT4 translocation in skeletal muscle would provide a novel treatment for type 2 diabetes mellitus. After a high-throughput screening (HTS) campaign and medicinal chemistry efforts, we identified the xanthene compound DS-1150b (16·tBuNH2) as a novel potent GLUT4 translocation enhancer. DS-1150b was found to promote GLUT4 translocation in L6-myotubes in rats and showed a glucose-lowering effect in an oral glucose tolerance test (oGTT) in a Zucker fatty rat model. Identification of naphthalene analog DS20060511 is also briefly described.

Keywords

DS-1150b; DS20060511; GLUT4; Glucose transporter 4; Translocation activator; Type 2 diabetes mellitus; Xanthene compound.

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