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TAK-875 CAS: 1000413-72-8

Category: Inhibitors
Product Name: TAK-875
Cat No: I000065
CAS No: 1000413-72-8
Synonyms: 2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid
Molecular Formula: C29H32O7S
Molecular Weight: 524.6
SMILES: CC1=C(C2=CC(COC3=CC=C([C@H](CC(O)=O)CO4)C4=C3)=CC=C2)C(C)=CC(OCCCS(C)(=O)=O)=C1
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
InChIKey: BZCALJIHZVNMGJ-HSZRJFAPSA-N
Solubility: DMSO: ≥ 158 mg/mL
Target: Free Fatty Acid Receptors
IC50: 0.072 μM(EC50)
Storage: Store at -20°C
CAS 1000413-72-8,TAK-875
  • Description

TAK-875 is a potent, selective and orally bioavailable GPR40 agonist with EC50 of 0.072 μM.
IC50 Value: 0.072 μM(EC50)
Target: GPR40
in vitro: TAK-875 exhibits potent agonist activity and high binding affinity to the human GPR40 receptor with Ki of 38 nM. TAK-875 displays weaker affinity toward the rat GPR40 receptor with Ki of 140 nM. TAK-875 displays excellent selectivity, as TAK-875 has little agonist potency to other members of the FFA receptor family with EC50 of >10 μM. TAK-875 treatment induces a concentration-dependent increase in intracellular IP production in CHO-hGPR40 with EC50 of 72 nM, more potently than that of endogenous ligand agonist oleic acid which requires much higher ligand concentrations to activate the receptor with EC50 of 29.9 μM. Neither TAK-875 nor oleic acid elicits an IP response in control CHO cells devoid of hGPR40.
in vivo: In type 2 diabetic N-STZ-1.5 rats, administration of TAK-875 (1-10 mg/kg p.o.) shows a clear improvement in glucose tolerance and augments insulin secretion. Additionally, TAK-875 (10 mg/kg, p.o.) significantly augments plasma insulin levels and reduces fasting hyperglycemia in male Zucker diabetic fatty rats, whereas in fasted normal Sprague-Dawley rats, TAK-875 neither enhances insulin secretion nor causes hypoglycemia even at 30 mg/kg.

  • Spec

Appearance:white to off-white solid powder
Purity: > 98%

  • References


1:Fasiglifam (TAK-875): Mechanistic Investigation and Retrospective Identification of Hazards for Drug Induced Liver Injury. Otieno MA, Snoeys J, Lam W, Ghosh A, Player MR, Pocai A, Salter R, Simic D, Skaggs H, Singh B, Lim HK.Toxicol Sci. 2017 Feb 16. doi: 10.1093/toxsci/kfx040. [Epub ahead of print] PMID: 28206647
2:Fasiglifam (TAK-875) Alters Bile Acid Homeostasis in Rats and Dogs: A Potential Cause of Drug Induced Liver Injury. Wolenski FS, Zhu AZX, Johnson M, Yu S, Moriya Y, Ebihara T, Csizmadia V, Grieves J, Paton M, Liao M, Gemski C, Pan L, Vakilynejad M, Dragan YP, Chowdhury SK, Kirby PJ.Toxicol Sci. 2017 May 1;157(1):50-61. doi: 10.1093/toxsci/kfx018. PMID: 28108665 Free PMC Article
3:Fasiglifam (TAK-875) has dual potentiating mechanisms via Gαq-GPR40/FFAR1 signaling branches on glucose-dependent insulin secretion. Sakuma K, Yabuki C, Maruyama M, Abiru A, Komatsu H, Negoro N, Tsujihata Y, Takeuchi K, Habata Y, Mori M.Pharmacol Res Perspect. 2016 Apr 27;4(3):e00237. doi: 10.1002/prp2.237. eCollection 2016 Jun. PMID: 27433346 Free PMC Article
4:Long-term safety and efficacy of fasiglifam (TAK-875), a G-protein-coupled receptor 40 agonist, as monotherapy and combination therapy in Japanese patients with type 2 diabetes: a 52-week open-label phase III study. Kaku K, Enya K, Nakaya R, Ohira T, Matsuno R.Diabetes Obes Metab. 2016 Sep;18(9):925-9. doi: 10.1111/dom.12693. Epub 2016 Jun 29. PMID: 27178047
5:Fasiglifam/TAK-875, a Selective GPR40 Agonist, Improves Hyperglycemia in Rats Unresponsive to Sulfonylureas and Acts Additively with Sulfonylureas. Ito R, Tsujihata Y, Suzuki M, Miyawaki K, Matsuda K, Takeuchi K.J Pharmacol Exp Ther. 2016 Apr;357(1):217-27. doi: 10.1124/jpet.115.230730. Epub 2016 Jan 26. PMID: 26813930 Free Article
6:Fasiglifam (TAK-875) Inhibits Hepatobiliary Transporters: A Possible Factor Contributing to Fasiglifam-Induced Liver Injury. Li X, Zhong K, Guo Z, Zhong D, Chen X.Drug Metab Dispos. 2015 Nov;43(11):1751-9. doi: 10.1124/dmd.115.064121. Epub 2015 Aug 14. PMID: 26276582 Free Article
7: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. Kaku K, Enya K, Nakaya R, Ohira T, Matsuno R.Diabetes Obes Metab. 2015 Jul;17(7):675-81. doi: 10.1111/dom.12467. Epub 2015 Apr 23. PMID: 25787200 Free PMC Article
8:High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Srivastava A, Yano J, Hirozane Y, Kefala G, Gruswitz F, Snell G, Lane W, Ivetac A, Aertgeerts K, Nguyen J, Jennings A, Okada K.Nature. 2014 Sep 4;513(7516):124-7. doi: 10.1038/nature13494. Epub 2014 Jul 20. PMID: 25043059
9:A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-allosteric modulator of FFAR1. Yabuki C, Komatsu H, Tsujihata Y, Maeda R, Ito R, Matsuda-Nagasumi K, Sakuma K, Miyawaki K, Kikuchi N, Takeuchi K, Habata Y, Mori M.PLoS One. 2013 Oct 10;8(10):e76280. doi: 10.1371/journal.pone.0076280. eCollection 2013. PMID: 24130766 Free PMC Article
10:Pharmacometric Approaches to Guide Dose Selection of the Novel GPR40 Agonist TAK-875 in Subjects With Type 2 Diabetes Mellitus. Naik H, Lu J, Cao C, Pfister M, Vakilynejad M, Leifke E.CPT Pharmacometrics Syst Pharmacol. 2013 Jan 9;2:e22. doi: 10.1038/psp.2012.23. PMID: 23887592 Free PMC Article


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