PMID- 30185729
OWN - NLM
STAT- MEDLINE
DCOM- 20190617
LR  - 20190618
IS  - 0015-5691 (Print)
IS  - 0015-5691 (Linking)
VI  - 152
IP  - 3
DP  - 2018
TI  - [The role of pharmacology to produce firuglipel (DS-8500a), an orally available 
      GPR119 agonist for type 2 diabetes mellitus].
PG  - 119-124
LID - 10.1254/fpj.152.119 [doi]
AB  - GPR119 (G-protein coupled receptor 119) has been shown to be highly expressed in 
      the lower small intestinal and colorectal L-cells and pancreatic beta-cells, and 
      mediates intracellular cAMP concentration, glucagon like peptide (GLP-1) 
      secretion, and glucose stimulated insulin secretion (GSIS). As the next 
      generation for the treatment of type 2 diabetes mellitus (T2DM), GPR119 agonist 
      has been intensively studied by pharmaceutical companies and a lot of patents 
      have been applied by them. In such highly competitive condition, biological 
      differentiation and to find an advantage among GPR119 agonists were necessary to 
      proceed the candidate compound in further clinical investigation. Firuglipel 
      (DS-8500a) is an orally available GPR119 agonist synthesized in DAIICHI SANKYO 
      CO., LTD (DS). It was originated from DS-chemical library and optimized in the 
      aspect of bioavailability and safety. Firuglipel had a higher intrinsic activity 
      (IA) of the production of intracellular cAMP in human GPR119 expressing CHO-K1 
      cells than those of other GPR119 agonists studied. The level of IA in each GPR119 
      agonist was correlated with the existence of agonist conformer. In parallel with 
      the study for the differentiation from other GPR119 agonists, we compared 
      firuglipel with dipeptidyl peptide-4 (DPP-4) inhibitor in NONcNZO10/LtJ mice and 
      evaluated their combination in streptozotocin (STZ) treated C57BL/6J mice to 
      clarify future positioning among anti-diabetics therapy. These pharmacological 
      studies illustrated here can draw out a clinical value of compound and expected 
      to lead the production of first-in-class agent in pharmaceutical companies.
FAU - Matsumoto, Koji
AU  - Matsumoto K
AD  - Daiichi Sankyo Co., Ltd.
FAU - Yoshitomi, Tomomi
AU  - Yoshitomi T
AD  - Daiichi Sankyo Co., Ltd.
FAU - Shimada, Takashi
AU  - Shimada T
AD  - Daiichi Sankyo RD Novare, Co., Ltd.
LA  - jpn
PT  - Journal Article
PL  - Japan
TA  - Nihon Yakurigaku Zasshi
JT  - Nihon yakurigaku zasshi. Folia pharmacologica Japonica
JID - 0420550
RN  - 0 (Benzamides)
RN  - 0 (Cyclopropanes)
RN  - 0 (GPR119 protein, human)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Oxadiazoles)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 08P99TX229 (firuglipel)
SB  - IM
MH  - Animals
MH  - Benzamides/*pharmacology
MH  - CHO Cells
MH  - Cricetulus
MH  - Cyclopropanes/*pharmacology
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Mice
MH  - Oxadiazoles/*pharmacology
MH  - Receptors, G-Protein-Coupled/agonists
EDAT- 2018/09/07 06:00
MHDA- 2019/06/18 06:00
CRDT- 2018/09/07 06:00
PHST- 2018/09/07 06:00 [entrez]
PHST- 2018/09/07 06:00 [pubmed]
PHST- 2019/06/18 06:00 [medline]
AID - 10.1254/fpj.152.119 [doi]
PST - ppublish
SO  - Nihon Yakurigaku Zasshi. 2018;152(3):119-124. doi: 10.1254/fpj.152.119.