1. GPCR/G Protein
  2. GPR40

TAK-875 (Synonyms: Fasiglifam)

Cat. No.: HY-10480 Purity: 98.77% ee.: 98.88%
Data Sheet SDS Handling Instructions

TAK-875 is a potent, selective and orally bioavailable GPR40 agonist with EC50 of 72 nM.

For research use only. We do not sell to patients.
TAK-875 Chemical Structure

TAK-875 Chemical Structure

CAS No. : 1000413-72-8

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $115 In-stock
2 mg $60 In-stock
5 mg $100 In-stock
10 mg $150 In-stock
50 mg $450 In-stock
100 mg $740 In-stock
200 mg $1240 In-stock
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    TAK-875 purchased from MCE. Usage Cited in: J Cell Biochem. 2017 May;118(5):1249-1261.

    Free fatty acid receptor 1 (FFAR1) agonist induces LOX-1 upregulation in cultured vascular smooth muscle cells (VSMCs). Cultured VSMCs are treated with synthetic agonists for either FFAR1 (TAK-875) or FFAR4 (TUG-891) at indicated doses for 24 hours. Both FFAR1 and FFAR4 are known responsible for long chain fatty acids. 0.1% DMSO is used as solvent control (SC). Western blotting detection indicates that treatment with agonistic action of FFAR1, but not FFAR4, remarkably upregulated LOX-1 expressi

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    • Biological Activity

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    • References

    Description

    TAK-875 is a potent, selective and orally bioavailable GPR40 agonist with EC50 of 72 nM.

    IC50 & Target

    EC50: 72 nM (GPR40)

    In Vitro

    TAK-875 (0.01-10 μM) produces a concentration-dependent increase in intracellular IP production in CHO-hGPR40, with EC50 of 0.072 μM. TAK-875 (0.1-10 μM) dose-dependently augments intracellular IP production in CHO cells[1]. TAK-875 (3-30 μM) concentration-dependently augments [Ca2+]i. In the presence of 10 mM glucose, TAK-875 (0.001-10 μM) dose-dependently stimulats insulin secretion from INS-1 833/15 cells[2].

    In Vivo

    TAK-875 (10 mg/kg, p.o.) increases plasma insulin levels in ZDF rats. TAK-875 (30 mg/kg, p.o.) improves fasting hyperglycemia without affecting fasting normoglycemia. TAK-875 at 30 mg/kg, which is a 3- to 10-fold higher dose compared with the dose that improved glucose tolerance in diabetic rats, does not alter fasting glucose levels in SD rats with normal glucose homeostasis. Likewise, TAK-875 does not significantly alter insulin secretion in SD rats with normal fasting glucose levels [1].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT01982253 Takeda Type 2 Diabetes Mellitus October 2013 Phase 2
    NCT02015780 Takeda Type 2 Diabetes Mellitus|Chronic Kidney Disease December 2013 Phase 3
    NCT01456195 Takeda Diabetes Mellitus, Type 2 November 2011 Phase 3
    NCT01834274 Takeda Diabetes Mellitus, Type 2 June 2013 Phase 3
    NCT01549964 Takeda Glycemic Control April 2012 Phase 3
    NCT01609582 Takeda Type 2 Diabetes|Cardiovascular Disease June 2012 Phase 3
    NCT01496443 Takeda Pharmacokinetics January 2012 Phase 1
    NCT01647542 Takeda Type 2 Diabetes Mellitus October 2012 Phase 3
    NCT00949091 Takeda Diabetes Mellitus, Type 2 January 2009 Phase 1
    NCT01829477 Takeda Diabetes Mellitus, Type 2 April 2013 Phase 3
    NCT01481116 Takeda Diabetes Mellitus, Type 2 January 2012 Phase 3
    NCT01829464 Takeda Diabetes May 2013 Phase 3
    NCT01433419 Takeda Diabetes Mellitus January 2012 Phase 3
    NCT01433406 Takeda Diabetes Mellitus October 2011 Phase 3
    NCT01414920 Takeda Diabetes Mellitus, Type 2 August 2011 Phase 2
    NCT01007097 Takeda Diabetes Mellitus, Type 2 December 2009 Phase 2
    NCT01433393 Takeda Diabetes Mellitus Phase 3
    NCT01585792 Takeda Diabetic Patients May 2012 Phase 3
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    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 1.9061 mL 9.5305 mL 19.0611 mL
    5 mM 0.3812 mL 1.9061 mL 3.8122 mL
    10 mM 0.1906 mL 0.9531 mL 1.9061 mL
    Kinase Assay
    [1]

    INS-1 832/13 cells are suspended in RPMI medium containing 11 mM glucose and the supplements described above. These cells are seeded at a density of 2×104 cells/well in a 96-well black plate coated with poly-D-lysine, and 1% BSA and 0.1% DMSO alone (control), palmitic acid (62.5, 125, 250, 500, and 1000 μM), oleic acid (62.5, 125, 250, 500, and 1000 μM), or TAK-875 (6.25, 12.5, 25, 50, and 100 μM) is added to the plate with 1% BSA and 0.1% DMSO, followed by culture for 72 h. After the culture, caspase 3/7 activity is measured with the Apo-one homogeneous caspase 3/7 assay according to the manufacturer's instructions. Fluorescence intensity is measured at an excitation of 485 nm and an emission at 535 nm. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    TAK-875 is dissolved in 1% BSA and 0.1% DMSO. 

    INS-1 832/13 cells are suspended in RPMI medium and seeded in a 96-well plate at a density of 2×104 cells/well; 1% BSA and 0.1% DMSO alone (control), palmitic acid (10, 100, and 1000 μM), oleic acid (10, 100, and 1000 μM), or TAK-875 (1, 10, and 100 μM) is added to the plate. After 72-h culture, medium is discarded, and cells are preincubated for 2 h with KRBH containing 1 mM glucose and 0.2% BSA at 37°C. After discarding of the preincubation buffer, KRBH containing 1 or 20 mM glucose and 0.2% BSA is added, and the plate is further incubated for 2 h. The insulin concentration in the supernatant is measured as described above. To measure intracellular insulin content, INS-1 832/13 cells are exposed to 1% BSA and 0.1% DMSO alone (control), palmitic acid (1000 μM), oleic acid (1000 μM), or TAK-875 (100 μM) with 1% BSA and 0.1% DMSO. After incubation, cells are washed once with phosphate-buffered saline, and acid-ethanol solution is added to each well, followed by sonication on ice. Intracellular insulin is extracted by overnight incubation at −30°C, followed by separation of supernatant by centrifugation at 12,000 rpm×5 min at 4°C. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    TAK-875 is formulated in 0.5% methylcellulose.

    At 18 weeks of age, the N-STZ-1.5 rats are fasted overnight and orally given vehicle (0.5% methylcellulose) or TAK-875 (1, 3, and 10 mg/kg). Sixty minutes later, all animals receive an oral glucose load (1 g/kg). Blood samples are collected from the tail vein before drug administration, before glucose load (time 0), and 10, 30, 60, and 120 min after the glucose load. Plasma glucose and insulin levels are measured with an AutoAnalyzer 7080 and radioimmunoassay, respectively. To see the effects of TAK-875 on fasting normoglycemia and hyperglycemia, SD rats (8 weeks old) or ZDF and ZL rats (12 weeks old) are fasted overnight and orally given vehicle (0.5% methylcellulose), TAK-875 (10 or 30 mg/kg), nateglinide (50 mg/kg), or glibenclamide (10 mg/kg). Blood samples are collected from the tail vein before drug administration (time 0) and 0.5, 1, 2, and 3 h (SD rats) and 0.5, 1, 2, 4, and 6 h (ZDF and ZL rats) after drug administration, and plasma glucose and insulin levels are measured as described above. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    524.63

    Formula

    C₂₉H₃₂O₇S

    CAS No.

    1000413-72-8

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 128 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 98.77% ee.: 98.88%

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    Product Name:
    TAK-875
    Cat. No.:
    HY-10480
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