Tel: 732-484-9848
Fax: 888-484-5008
Email: sales@chemscene.com
   
Buliding blocks
Intermediates
Bioactive molecules
Product Pathways
All Targets
Anti-infection
Antibody-drug conjugate....
Apoptosis
Cell Cycle/DNA Damage
GPCR/G protein
Immunology/Inflammation
JAK/STAT Signaling
MAPK/ERK Pathway
Membrane Transporter/Io....
Metabolism/Protease
Microbiology
Neuronal Signaling
NF-KB
Others
PI3K/Akt/mTOR
Protein Tyrosine Kinase....
TGF-beta/Smad
Vitamin D Related
Wnt/Hedgehog/Notch
Research Area
Cancer
Cardiovascular Disease
Endocrinology
Infection
Metabolic Disease
Neurological Disease
Others
Inflammation/Immunology
Product Type
All Products
New Products
Featured Products
Home   »   Product Pathways  »  Endocrinology  »  TAK-875

Products are for research use only. Not for human use. We do not sell to patients.


CS-0282 TAK-875


(TAK 875;TAK875)
Structure Price and Availability of    TAK-875
United States
Size Price Stock
5mg $176 In-stock Inquiry
1g Get quote
5g Get quote
>10g Get quote
Inquiry for price and availability only. Please place your order via our email or fax.
Contact us for competitive discounts on bulk quantities .
  • Data Sheet
  • Introduction
  • References
  • Related Products

TAK-875  M.Wt: 524.64
TAK-875  Formula: C29H32O7S
TAK-875  Solubility: DMSO ≥100mg/mL Water <1.2mg/mL Ethanol ≥10mg/mL
TAK-875  Purity: >98%
TAK-875  Storage:  Please store the product under the recommended conditions in the Certificate of Analysis.
CAS: 1000413-72-8

View current batch:

TAK-875 is a potent, selective and orally bioavailable GPR40 agonist with EC50 of 0.072 μM. In treatment of diabetes.

1 . Tsujihata Y, Ito R, Suzuki M, Harada A, Negoro N, Yasuma T, Momose Y, Takeuchi K.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.J Pharmacol Exp Ther. 2011 Oct;339(1):228-37. Epub 2011 Jul 13.
Abstract
G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA(1)) is highly expressed in pancreatic β cells and mediates free fatty acid-induced insulin secretion. This study examined the pharmacological effects and potential for avoidance of lipotoxicity of [(3S)-6-({2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}meth-oxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid hemi-hydrate) (TAK-875), a novel, orally available, selective GPR40 agonist. Insulinoma cell lines and primary rat islets were used to assess the effects of TAK-875 in vitro. The in vivo effects of TAK-875 on postprandial hyperglycemia, fasting hyperglycemia, and normoglycemia were examined in type 2 diabetic and normal rats. In rat insulinoma INS-1 833/15 cells, TAK-875 increased intracellular inositol monophosphate and calcium concentration, consistent with activation of the Gqα signaling pathway. The insulinotropic action of TAK-875 (10 μM) in INS-1 833/15 and primary rat islets was glucose-dependent. Prolonged exposure of cytokine-sensitive INS-1 832/13 to TAK-875 for 72 h at pharmacologically active concentrations did not alter glucose-stimulated insulin secretion, insulin content, or caspase 3/7 activity, whereas prolonged exposure to palmitic or oleic acid impaired β cell function and survival. In an oral glucose tolerance test in type 2 diabetic N-STZ-1.5 rats, TAK-875 (1-10 mg/kg p.o.) showed a clear improvement in glucose tolerance and augmented insulin secretion. In addition, TAK-875 (10 mg/kg, p.o.) significantly augmented plasma insulin levels and reduced fasting hyperglycemia in male Zucker diabetic fatty rats, whereas in fasted normal Sprague-Dawley rats, TAK-875 neither enhanced insulin secretion nor caused hypoglycemia even at 30 mg/kg. TAK-875 enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia with a low risk of hypoglycemia and no evidence of β cell toxicity.

2 . Yashiro H, Tsujihata Y, Takeuchi K, Hazama M, Johnson PR, Rorsman P.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.J Pharmacol Exp Ther. 2012 Feb;340(2):483-9. Epub 2011 Nov 21.
Abstract
G protein-coupled receptor 40 (GPR40)/free fatty acid 1 (FFA1) is a G protein-coupled receptor involved in free fatty acid-induced insulin secretion. To analyze the effect of our novel GPR40/FFA1-selective agonist, [(3S)-6-({2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid hemi-hydrate (TAK-875), on insulin and glucagon secretion, we performed hormone secretion assays and measured intracellular Ca2? concentration ([Ca2?](i)) in both human and rat islets. Insulin and glucagon secretion were measured in static and dynamic conditions by using groups of isolated rat and human pancreatic islets. [Ca2?](i) was recorded by using confocal microscopy. GPR40/FFA1 expression was measured by quantitative polymerase chain reaction. In both human and rat islets, TAK-875 enhanced glucose-induced insulin secretion in a glucose-dependent manner. The stimulatory effect of TAK-875 was similar to that produced by glucagon-like peptide-1 and correlated with the elevation of β-cell [Ca2?](i). TAK-875 was without effect on glucagon secretion at both 1 and 16 mM glucose in human islets. These data indicate that GPR40/FFA1 influences mainly insulin secretion in a glucose-dependent manner. The β-cell-specific action of TAK-875 in human islets may represent a therapeutically useful feature that allows plasma glucose control without compromising counter-regulation of glucagon secretion, thus minimizing the risk of hypoglycemia.

3 . Burant CF, Viswanathan P, Marcinak J, Cao C, Vakilynejad M, Xie B, Leifke E.TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial.Lancet. 2012 Apr 14;379(9824):1403-11. Epub 2012 Feb 27.
Abstract
BACKGROUND: Activation of free fatty acid receptor 1 (FFAR1; also known as G-protein-coupled receptor 40) by fatty acids stimulated glucose-dependent β-cell insulin secretion in preclinical models. We aimed to assess whether selective pharmacological activation of this receptor by TAK-875 in patients with type 2 diabetes mellitus improved glycaemic control without hypoglycaemia risk. METHODS: We undertook a phase 2, randomised, double-blind, and placebo-controlled and active-comparator-controlled trial in outpatients with type 2 diabetes who had not responded to diet or metformin treatment. Patients were randomly assigned equally to receive placebo, TAK-875 (6·25, 25, 50, 100, or 200 mg), or glimepiride (4 mg) once daily for 12 weeks. Patients and investigators were masked to treatment assignment. The primary outcome was change in haemoglobin A(1c) (HbA(1c)) from baseline. Analysis included all patients randomly assigned to treatment groups who received at least one dose of double-blind study drug. The trial is registered at ClinicalTrials.gov, NCT01007097...

4 . Leifke E, Naik H, Wu J, Viswanathan P, Demanno D, Kipnes M, Vakilynejad M.A multiple-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics of a novel GPR40 agonist, TAK-875, in subjects with type 2 diabetes.Clin Pharmacol Ther. 2012 Jul;92(1):29-39.
Abstract
G-protein-coupled receptor 40 (GPR40), highly expressed in pancreatic β-cells, mediates free fatty acid (FFA)-induced insulin secretion. This phase I, double-blind, randomized study investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel, glucose-lowering GPR40 agonist, TAK-875 (q.d., orally × 14 days), in type 2 diabetics (placebo, n = 14; at 25, 50, 100, 200, or 400 mg, n = 45). Approximately dose-proportional increases in AUC(0-24) and C(max) occurred. TAK-875 showed good tolerability with no dose-limiting side effects. Two subjects (on TAK-875) had mild hypoglycemia, probably related to prolonged fasting after oral glucose tolerance tests (OGTTs). TAK-875 showed reductions from baseline in fasting (2 to -93 mg/dl) and post-OGTT glucose (26 to -172 mg/dl), with an apparent dose-dependent increase in post-OGTT C-peptide over 14 days. Consistent with preclinical data, TAK-875 apparently acts as a glucose-dependent insulinotropic agent with low hypoglycemic risk. Its PK is suitable for once-daily oral administration.

5 . Yoshiyuki Tsujihata et al. TAK-875, an Orally Available GPR40/FFA1 Agonist Enhances Glucose-Dependent Insulin Secretion and Improves Both Postprandial and Fasting Hyperglycemia in Type 2 Diabetic Rats. JPET July 13, 2011
Abstract
GPR40/FFA1 is highly expressed in pancreatic β cells and mediates free fatty acid-induced insulin secretion. This study examined the pharmacological effects and potential for avoidance of lipotoxicity of TAK-875, a novel, orally available, selective GPR40 agonist. Insulinoma cell lines and primary rat islets were used to assess the effects of TAK-875 in vitro. The in vivo effects of TAK-875 on postprandial hyperglycemia, fasting hyperglycemia and normoglycemia were examined in type 2 diabetic and normal rats. In rat insulinoma INS-1 833/15 cells, TAK-875 increased intracellular inositol monophosphate and calcium concentration, consistent with activation of the Gqα signaling pathway. The insulinotropic action of TAK-875 (10 μM) in INS-1 833/15 and primary rat islets was glucose dependent....

GPR40  |  
Keywords: buy TAK-875 | TAK-875 Supplier | purchase TAK-875 | TAK-875 cost | TAK-875 manufacturer | order TAK-875 | TAK-875 distributor | TAK-875 structure,chemscene
buy 1000413-72-8 | 1000413-72-8 Supplier | purchase 1000413-72-8 | 1000413-72-8 cost | 1000413-72-8 manufacturer | order 1000413-72-8 | 1000413-72-8 distributor | 1000413-72-8 structure,chemscene


CHEMSCENE, LLC
Tel: 732-484-9848
Fax: 888-484-5008
Email:  sales@chemscene.com
Address: 11 Deer Park Drive, Suite 102D Monmouth Junction, NJ 08852.
Products are for research use only. Not for human use. We do not sell to patients. Sitemap | Inhibitor © Copyright 2012. All Rights Reserved.