TAK-875 (BioDeep_00000771848)
代谢物信息卡片
Fasiglifam
化学式: C29H32O7S (524.1868642)
中文名称: TAK875-消旋体
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: CC1=CC(=CC(=C1C2=CC=CC(=C2)COC3=CC4=C(C=C3)C(CO4)CC(=O)O)C)OCCCS(=O)(=O)C
InChI: InChI=1S/C29H32O7S/c1-19-12-25(34-10-5-11-37(3,32)33)13-20(2)29(19)22-7-4-6-21(14-22)17-35-24-8-9-26-23(15-28(30)31)18-36-27(26)16-24/h4,6-9,12-14,16,23H,5,10-11,15,17-18H2,1-3H3,(H,30,31)/t23-/m1/s1
描述信息
C78276 - Agent Affecting Digestive System or Metabolism > C29711 - Anti-diabetic Agent
同义名列表
2 个代谢物同义名
数据库引用编号
6 个数据库交叉引用编号
- ChEBI: CHEBI:177451
- KEGGdrug: D10336
- PubChem: 24857286
- DrugBank: DB12491
- ChEMBL: CHEMBL1829174
- CAS: 1000413-72-8
分类词条
相关代谢途径
Reactome(0)
BioCyc(0)
PlantCyc(0)
代谢反应
0 个相关的代谢反应过程信息。
Reactome(0)
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(0)
PharmGKB(0)
0 个相关的物种来源信息
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：
- PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。
文献列表
- Zongtao Zhou, Qiang Ren, Shixuan Jiao, Zongyu Cai, Xinqian Geng, Liming Deng, Bin Wang, Lijun Hu, Luyong Zhang, Ying Yang, Zheng Li. Discovery of new and highly effective quadruple FFA1 and PPARα/γ/δ agonists as potential anti-fatty liver agents.
European journal of medicinal chemistry.
2022 Feb; 229(?):114061. doi:
10.1016/j.ejmech.2021.114061. [PMID: 34954593] - Merrie Mosedale, Yanwei Cai, J Scott Eaddy, Patrick J Kirby, Francis S Wolenski, Yvonne Dragan, William Valdar. Human-relevant mechanisms and risk factors for TAK-875-Induced liver injury identified via a gene pathway-based approach in Collaborative Cross mice.
Toxicology.
2021 09; 461(?):152902. doi:
10.1016/j.tox.2021.152902. [PMID: 34418498] - Zheng Li, Zongtao Zhou, Lijun Hu, Liming Deng, Qiang Ren, Luyong Zhang. ZLY032, the first-in-class dual FFA1/PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosis.
Pharmacological research.
2020 09; 159(?):105035. doi:
10.1016/j.phrs.2020.105035. [PMID: 32562818] - Yugang Yan, Qifu Xu, Chunlong Zhao, Hang Dong, Wenfang Xu, Yingjie Zhang. In vivo pharmacokinetic study and oral glucose tolerance test of sulfoxide analogs of GPR40 agonist TAK-875.
Drug development research.
2020 09; 81(6):708-715. doi:
10.1002/ddr.21675. [PMID: 32359092] - Edyta Gendaszewska-Darmach, Anna Drzazga, Maria Koziołkiewicz. Targeting GPCRs Activated by Fatty Acid-Derived Lipids in Type 2 Diabetes.
Trends in molecular medicine.
2019 10; 25(10):915-929. doi:
10.1016/j.molmed.2019.07.003. [PMID: 31377146] - Zheng Li, Chunxia Liu, Jianyong Yang, Jiaqi Zhou, Zhiwen Ye, Dazhi Feng, Na Yue, Jiayi Tong, Wenlong Huang, Hai Qian. Design, synthesis and biological evaluation of novel FFA1/GPR40 agonists: New breakthrough in an old scaffold.
European journal of medicinal chemistry.
2019 Oct; 179(?):608-622. doi:
10.1016/j.ejmech.2019.06.087. [PMID: 31279294] - Xuekun Wang, Yurui Xu, Shujun Feng, Xinyu Huang, Xia Meng, Jiao Chen, Leilei Guo, Junliang Ge, Jikang Zhang, Jianmei Chen, Li Cheng, Kai Gu, Yu Zhang, Qing Jiang, Xinghai Ning. A potent free fatty acid receptor 1 agonist with a glucose-dependent antihyperglycemic effect.
Chemical communications (Cambridge, England).
2019 Aug; 55(61):8975-8978. doi:
10.1039/c9cc04040d. [PMID: 31290492] - Michael Lückmann, Mette Trauelsen, Marie A Bentsen, Tinne A D Nissen, Joao Martins, Zohreh Fallah, Mads M Nygaard, Elena Papaleo, Kresten Lindorff-Larsen, Thue W Schwartz, Thomas M Frimurer. Molecular dynamics-guided discovery of an ago-allosteric modulator for GPR40/FFAR1.
Proceedings of the National Academy of Sciences of the United States of America.
2019 04; 116(14):7123-7128. doi:
10.1073/pnas.1811066116. [PMID: 30872479] - Akifumi Kogame, Ronald Lee, Liping Pan, Miyako Sudo, Masami Nonaka, Yuu Moriya, Tomoaki Higuchi, Yoshihiko Tagawa. Disposition and metabolism of the G protein-coupled receptor 40 agonist TAK-875 (fasiglifam) in rats, dogs, and humans.
Xenobiotica; the fate of foreign compounds in biological systems.
2019 Apr; 49(4):433-445. doi:
10.1080/00498254.2018.1453100. [PMID: 29557709] - Yongzai Qiang, Xiaohui Zhang. Pharmacokinetics of TAK-875 and its toxic metabolite TAK-875- acylglucuronide in rat plasma by liquid chromatography tandem mass spectrometry.
Biomedical chromatography : BMC.
2019 Mar; 33(3):e4441. doi:
10.1002/bmc.4441. [PMID: 30456906] - Zheng Li, Yueming Chen, Zongtao Zhou, Liming Deng, Yawen Xu, Lijun Hu, Bing Liu, Luyong Zhang. Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agents.
European journal of medicinal chemistry.
2019 Feb; 164(?):352-365. doi:
10.1016/j.ejmech.2018.12.069. [PMID: 30605833] - Yuya Urano, Shingo Oda, Koichi Tsuneyama, Tsuyoshi Yokoi. Comparative hepatic transcriptome analyses revealed possible pathogenic mechanisms of fasiglifam (TAK-875)-induced acute liver injury in mice.
Chemico-biological interactions.
2018 Dec; 296(?):185-197. doi:
10.1016/j.cbi.2018.09.011. [PMID: 30243991] - John Marcinak, Majid Vakilynejad, Akifumi Kogame, Yoshihiko Tagawa. Evaluation of the Pharmacokinetics and Safety of a Single Oral Dose of Fasiglifam in Subjects with Mild or Moderate Hepatic Impairment.
Drugs in R&D.
2018 Jun; 18(2):109-118. doi:
10.1007/s40268-018-0229-9. [PMID: 29488154] - John F Marcinak, Melvin S Munsaka, Paul B Watkins, Takashi Ohira, Neila Smith. Liver Safety of Fasiglifam (TAK-875) in Patients with Type 2 Diabetes: Review of the Global Clinical Trial Experience.
Drug safety.
2018 06; 41(6):625-640. doi:
10.1007/s40264-018-0642-6. [PMID: 29492878] - Joseph D Ho, Betty Chau, Logan Rodgers, Frances Lu, Kelly L Wilbur, Keith A Otto, Yanyun Chen, Min Song, Jonathan P Riley, Hsiu-Chiung Yang, Nichole A Reynolds, Steven D Kahl, Anjana Patel Lewis, Christopher Groshong, Russell E Madsen, Kris Conners, Jayana P Lineswala, Tarun Gheyi, Melbert-Brian Decipulo Saflor, Matthew R Lee, Jordi Benach, Kenton A Baker, Chahrzad Montrose-Rafizadeh, Michael J Genin, Anne R Miller, Chafiq Hamdouchi. Structural basis for GPR40 allosteric agonism and incretin stimulation.
Nature communications.
2018 04; 9(1):1645. doi:
10.1038/s41467-017-01240-w. [PMID: 29695780] - Zheng Li, Chunxia Liu, Wei Shi, Xingguang Cai, Yuxuan Dai, Chen Liao, Wenlong Huang, Hai Qian. Identification of highly potent and orally available free fatty acid receptor 1 agonists bearing isoxazole scaffold.
Bioorganic & medicinal chemistry.
2018 02; 26(3):703-711. doi:
10.1016/j.bmc.2017.12.030. [PMID: 29291938] - Zheng Li, Xue Xu, Gang Li, Xiaoting Fu, Yanzhi Liu, Yufeng Feng, Mingyan Wang, Yunting Ouyang, Jing Han. Improving metabolic stability with deuterium: The discovery of GPU-028, a potent free fatty acid receptor 4 agonists.
Bioorganic & medicinal chemistry.
2017 12; 25(24):6647-6652. doi:
10.1016/j.bmc.2017.10.040. [PMID: 29100735] - Xuejun V Peng, John F Marcinak, Marsha G Raanan, Charlie Cao. Combining the G-protein-coupled receptor 40 agonist fasiglifam with sitagliptin improves glycaemic control in patients with type 2 diabetes with or without metformin: A randomized, 12-week trial.
Diabetes, obesity & metabolism.
2017 08; 19(8):1127-1134. doi:
10.1111/dom.12921. [PMID: 28239939] - Francis S Wolenski, Andy Z X Zhu, Mike Johnson, Shaoxia Yu, Yuu Moriya, Takuya Ebihara, Vilmos Csizmadia, Jessica Grieves, Martin Paton, Mingxiang Liao, Christopher Gemski, Liping Pan, Majid Vakilynejad, Yvonne P Dragan, Swapan K Chowdhury, Patrick J Kirby. Fasiglifam (TAK-875) Alters Bile Acid Homeostasis in Rats and Dogs: A Potential Cause of Drug Induced Liver Injury.
Toxicological sciences : an official journal of the Society of Toxicology.
2017 05; 157(1):50-61. doi:
10.1093/toxsci/kfx018. [PMID: 28108665] - Jeppe H Ekberg, Maria Hauge, Line V Kristensen, Andreas N Madsen, Maja S Engelstoft, Anna-Sofie Husted, Rasmus Sichlau, Kristoffer L Egerod, Pascal Timshel, Timothy J Kowalski, Fiona M Gribble, Frank Reiman, Harald S Hansen, Andrew D Howard, Birgitte Holst, Thue W Schwartz. GPR119, a Major Enteroendocrine Sensor of Dietary Triglyceride Metabolites Coacting in Synergy With FFA1 (GPR40).
Endocrinology.
2016 Dec; 157(12):4561-4569. doi:
10.1210/en.2016-1334. [PMID: 27779915] - Liang Ma, Taijin Wang, Min Shi, Ping Fu, Heying Pei, Haoyu Ye. Synthesis, Activity, and Docking Study of Novel Phenylthiazole-Carboxamido Acid Derivatives as FFA2 Agonists.
Chemical biology & drug design.
2016 07; 88(1):26-37. doi:
10.1111/cbdd.12729. [PMID: 26808470] - Hodaka Yamada, Masashi Yoshida, Kiyonori Ito, Katsuya Dezaki, Toshihiko Yada, San-E Ishikawa, Masafumi Kakei. Potentiation of Glucose-stimulated Insulin Secretion by the GPR40-PLC-TRPC Pathway in Pancreatic β-Cells.
Scientific reports.
2016 05; 6(?):25912. doi:
10.1038/srep25912. [PMID: 27180622] - Xiao-Min Ren, Lin-Ying Cao, Jing Zhang, Wei-Ping Qin, Yu Yang, Bin Wan, Liang-Hong Guo. Investigation of the Binding Interaction of Fatty Acids with Human G Protein-Coupled Receptor 40 Using a Site-Specific Fluorescence Probe by Flow Cytometry.
Biochemistry.
2016 Apr; 55(13):1989-96. doi:
10.1021/acs.biochem.6b00079. [PMID: 26974599] - Ryo Ito, Yoshiyuki Tsujihata, Masami Suzuki, Kazumasa Miyawaki, Kae Matsuda, Koji Takeuchi. Fasiglifam/TAK-875, a Selective GPR40 Agonist, Improves Hyperglycemia in Rats Unresponsive to Sulfonylureas and Acts Additively with Sulfonylureas.
The Journal of pharmacology and experimental therapeutics.
2016 Apr; 357(1):217-27. doi:
10.1124/jpet.115.230730. [PMID: 26813930] - Xiuli Li, Kan Zhong, Zitao Guo, Dafang Zhong, Xiaoyan Chen. Fasiglifam (TAK-875) Inhibits Hepatobiliary Transporters: A Possible Factor Contributing to Fasiglifam-Induced Liver Injury.
Drug metabolism and disposition: the biological fate of chemicals.
2015 Nov; 43(11):1751-9. doi:
10.1124/dmd.115.064121. [PMID: 26276582] - K Kaku, K Enya, R Nakaya, T Ohira, R Matsuno. Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial.
Diabetes, obesity & metabolism.
2015 Jul; 17(7):675-81. doi:
10.1111/dom.12467. [PMID: 25787200] - Michael Mayer, Sai Nudurupati, Xuejun Peng, John Marcinak. Evaluation of the pharmacokinetics and safety of a single oral dose of fasiglifam in subjects with normal or varying degrees of impaired renal function.
Drugs in R&D.
2014 Dec; 14(4):273-82. doi:
10.1007/s40268-014-0066-4. [PMID: 25374042] - Ankita Srivastava, Jason Yano, Yoshihiko Hirozane, Georgia Kefala, Franz Gruswitz, Gyorgy Snell, Weston Lane, Anthony Ivetac, Kathleen Aertgeerts, Jasmine Nguyen, Andy Jennings, Kengo Okada. High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875.
Nature.
2014 Sep; 513(7516):124-7. doi:
10.1038/nature13494. [PMID: 25043059] - Yoshihiko Hirozane, Takashi Motoyaji, Takamitsu Maru, Kengo Okada, Naoki Tarui. Generating thermostabilized agonist-bound GPR40/FFAR1 using virus-like particles and a label-free binding assay.
Molecular membrane biology.
2014 Aug; 31(5):168-75. doi:
10.3109/09687688.2014.923588. [PMID: 25068810] - R Ito, Y Tsujihata, K Matsuda-Nagasumi, I Mori, N Negoro, K Takeuchi. TAK-875, a GPR40/FFAR1 agonist, in combination with metformin prevents progression of diabetes and β-cell dysfunction in Zucker diabetic fatty rats.
British journal of pharmacology.
2013 Oct; 170(3):568-80. doi:
10.1111/bph.12297. [PMID: 23848179] - Chiori Yabuki, Hidetoshi Komatsu, Yoshiyuki Tsujihata, Risa Maeda, Ryo Ito, Kae Matsuda-Nagasumi, Kensuke Sakuma, Kazumasa Miyawaki, Naoya Kikuchi, Koji Takeuchi, Yugo Habata, Masaaki Mori. A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-allosteric modulator of FFAR1.
PloS one.
2013; 8(10):e76280. doi:
10.1371/journal.pone.0076280. [PMID: 24130766] - Xiao-Tao Feng, Jing Leng, Zhen Xie, Shuang-Lei Li, Wei Zhao, Qian-Li Tang. GPR40: a therapeutic target for mediating insulin secretion (review).
International journal of molecular medicine.
2012 Dec; 30(6):1261-6. doi:
10.3892/ijmm.2012.1142. [PMID: 23023155] - Himanshu Naik, Majid Vakilynejad, Jingtao Wu, Prabhakar Viswanathan, Nobuhito Dote, Tomoaki Higuchi, Eckhard Leifke. Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of the GPR40 agonist TAK-875: results from a double-blind, placebo-controlled single oral dose rising study in healthy volunteers.
Journal of clinical pharmacology.
2012 Jul; 52(7):1007-16. doi:
10.1177/0091270011409230. [PMID: 21610201] - Nobuyuki Negoro, Shinobu Sasaki, Satoshi Mikami, Masahiro Ito, Yoshiyuki Tsujihata, Ryo Ito, Masami Suzuki, Koji Takeuchi, Nobuhiro Suzuki, Junichi Miyazaki, Takashi Santou, Tomoyuki Odani, Naoyuki Kanzaki, Miyuki Funami, Akio Morohashi, Masami Nonaka, Shinichiro Matsunaga, Tsuneo Yasuma, Yu Momose. Optimization of (2,3-dihydro-1-benzofuran-3-yl)acetic acids: discovery of a non-free fatty acid-like, highly bioavailable G protein-coupled receptor 40/free fatty acid receptor 1 agonist as a glucose-dependent insulinotropic agent.
Journal of medicinal chemistry.
2012 Apr; 55(8):3960-74. doi:
10.1021/jm300170m. [PMID: 22490067] - T Araki, M Hirayama, S Hiroi, K Kaku. GPR40-induced insulin secretion by the novel agonist TAK-875: first clinical findings in patients with type 2 diabetes.
Diabetes, obesity & metabolism.
2012 Mar; 14(3):271-8. doi:
10.1111/j.1463-1326.2011.01525.x. [PMID: 22051148] - Hiroaki Yashiro, Yoshiyuki Tsujihata, Koji Takeuchi, Masatoshi Hazama, Paul R V Johnson, Patrik Rorsman. The effects of TAK-875, a selective G protein-coupled receptor 40/free fatty acid 1 agonist, on insulin and glucagon secretion in isolated rat and human islets.
The Journal of pharmacology and experimental therapeutics.
2012 Feb; 340(2):483-9. doi:
10.1124/jpet.111.187708. [PMID: 22106100] - Yoshiyuki Tsujihata, Ryo Ito, Masami Suzuki, Ayako Harada, Nobuyuki Negoro, Tsuneo Yasuma, Yu Momose, Koji Takeuchi. TAK-875, an orally available G protein-coupled receptor 40/free fatty acid receptor 1 agonist, enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia in type 2 diabetic rats.
The Journal of pharmacology and experimental therapeutics.
2011 Oct; 339(1):228-37. doi:
10.1124/jpet.111.183772. [PMID: 21752941] - Nobuyuki Negoro, Shinobu Sasaki, Satoshi Mikami, Masahiro Ito, Masami Suzuki, Yoshiyuki Tsujihata, Ryo Ito, Ayako Harada, Koji Takeuchi, Nobuhiro Suzuki, Junichi Miyazaki, Takashi Santou, Tomoyuki Odani, Naoyuki Kanzaki, Miyuki Funami, Toshimasa Tanaka, Akifumi Kogame, Shinichiro Matsunaga, Tsuneo Yasuma, Yu Momose. Discovery of TAK-875: A Potent, Selective, and Orally Bioavailable GPR40 Agonist.
ACS medicinal chemistry letters.
2010 Sep; 1(6):290-4. doi:
10.1021/ml1000855. [PMID: 24900210] - Yasuaki Itoh, Yuji Kawamata, Masataka Harada, Makoto Kobayashi, Ryo Fujii, Shoji Fukusumi, Kazuhiro Ogi, Masaki Hosoya, Yasuhiro Tanaka, Hiroshi Uejima, Hideyuki Tanaka, Minoru Maruyama, Rie Satoh, Shoichi Okubo, Hideki Kizawa, Hidetoshi Komatsu, Fumika Matsumura, Yuko Noguchi, Tokuyuki Shinohara, Shuji Hinuma, Yukio Fujisawa, Masahiko Fujino. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40.
Nature.
2003 Mar; 422(6928):173-6. doi:
10.1038/nature01478. [PMID: 12629551]