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Imeglimin

Cat No.:V6419 Purity: ≥98%
Imeglimin (EMD 387008) is an oral hypoglycemic agent.
Imeglimin
Imeglimin Chemical Structure CAS No.: 775351-65-0
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
50mg
Other Sizes

Other Forms of Imeglimin:

  • Imeglimin HCl
Official Supplier of:
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Top Publications Citing lnvivochem Products
Product Description
Imeglimin (EMD 387008) is an oral hypoglycemic agent. Imeglimin improves insulin sensitivity. Imeglimin also reduces the production of reactive oxygen species (ROS), increases mitochondrial DNA, and improves mitochondrial function.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
Tert-butyl hydroperoxide (tBH)-induced cell death is totally prevented by preincubation with imeglimin (10 mM for 4 hours or 100 μM for 24 hours) [2].
ln Vivo
During the final six weeks of HFHSD feeding, meglimin (200 mg/kg b.i.d. oral) dramatically lowers hyperglycemia, returns normal glucose tolerance, and enhances insulin sensitivity [1].
Cell Assay
Cell Viability Assay [2]
Cell Types: Human Endothelial Cells (HMEC-1)
Tested Concentrations: 100 μM and 10 mM
Incubation Duration: 100 μM 24 hrs (hours), 10 mM 4 hrs (hours)
Experimental Results: Prevents cell death.
Animal Protocol
Animal/Disease Models: Male C57BL/6JOlaHsd mice (4 weeks old) [1]
Doses: 200 mg/kg
Route of Administration: po (oral gavage); bid; 6 weeks
Experimental Results: A slight decrease in body weight and food intake was observed, and There is some diarrhea, but only during the first few days of treatment.
References

[1]. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrialfunction in liver of a high-fat, high-sucrose diet mice model. Diabetes. 2015 Jun;64(6):2254-64.

[2]. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. Cell Death Discov. 2016 Jan 18;2:15072.

Additional Infomation
Imeglimin has been used in trials studying the treatment of Type 2 Diabetes Mellitus.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Exact Mass
155.117
CAS #
775351-65-0
Related CAS #
Imeglimin hydrochloride;775351-61-6
PubChem CID
24812808
Appearance
Typically exists as solid at room temperature
LogP
-1
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
2
Rotatable Bond Count
1
Heavy Atom Count
11
Complexity
205
Defined Atom Stereocenter Count
1
SMILES
C[C@@H]1N=C(NC(=N1)N(C)C)N
InChi Key
GFICWFZTBXUVIG-SCSAIBSYSA-N
InChi Code
InChI=1S/C6H13N5/c1-4-8-5(7)10-6(9-4)11(2)3/h4H,1-3H3,(H3,7,8,9,10)/t4-/m1/s1
Chemical Name
(4R)-6-N,6-N,4-trimethyl-1,4-dihydro-1,3,5-triazine-2,6-diamine
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
Durable Effect of Imeglimin on the Glycemic Control in Patients With Type 2 Diabetes Mellitus
CTID: NCT05366868
Phase: Phase 4    Status: Recruiting
Date: 2023-11-09
Pharmacokinetics of Imeglimin in Hepatic Impaired Subjects
CTID: NCT03802786
Phase: Phase 1    Status: Completed
Date: 2020-08-11
Bioequivalence of Imeglimin Tablet Formulations
CTID: NCT03646331
Phase: Phase 1    Status: Completed
Date: 2019-01-11
Effect of Cimetidine on the PK of Imeglimin
CTID: NCT03618316
Phase: Phase 1    Status: Completed
Date: 2018-08-27
Randomized, double-blind, placebo-controlled, parallel-group study of the safety and efficacy of imeglimin or placebo add-on therapy in type 2 diabetic subjects not adequately controlled by metformin monotherapy
CTID: null
Phase: Phase 2    Status: Completed
Date: 2010-06-11
A double-blind, double-dummy, randomized, controlled, multi-centre study of the activity and safety of 2 daily doses of EMD 387008 versus placebo and metformin in parallel groups after 8 weeks of treatment in type 2 diabetic subjects.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2006-07-21
Study for the effects of imeglimin on glycemic control in patients with type 2 diabetes
CTID: jRCT1011220005
Phase:    Status: Recruiting
Date: 2022-05-11
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Imeglimin add-on therapy:A randomized, double-blind, clinical trial
CTID: jRCTs061210082
Phase:    Status: Recruiting
Date: 2022-03-04


Mechanism of Imeglimin effect on glucose metabolism by a 75g oral glucose tolerance test with double-tracer
CTID: jRCTs031210600
Phase:    Status: Recruiting
Date: 2022-02-07
Study to evaluate intestinal glucose excretion using 18F-FDG-PET/MR enterography in patients taking imeglimin
CTID: UMIN000045345
Phase:    Status: Pending
Date: 2021-10-01
The Pharmacokinetics study of Imeglimin (PXL008) in Japanese Subjects with Renal Impairment
CTID: jRCT2080224682
Phase:    Status: completed
Date: 2019-05-10
TIMES 3
CTID: jRCT2080223790
Phase:    Status: completed
Date: 2018-01-30
TIMES 2
CTID: jRCT2080223726
Phase:    Status: completed
Date: 2017-11-22
TIMES 1
CTID: jRCT2080223713
Phase:    Status: completed
Date: 2017-11-13
None
CTID: jRCT2080223032
Phase:    Status:
Date: 2015-12-01

Biological Data
  • Effect of Imeglimin on tBH- or hyperglycemia-induced endothelial cell death. HMEC-1 cells incubated in the absence or presence of either 100 μM Imeglimin for 24 h, 10 mM Imeglimin for 4 h or 1 μM CsA for 30 min were washed with PBS before subsequent exposure to 0.5 mM tBH or vehicle (control) in FBS-free culture medium for 45 min. Cells were then washed with PBS and incubated at 37 °C for 24 h in a complete MCDB medium. Alternatively, HMEC-1 cells were cultured for 48 h in a complete MCDB medium at the indicated concentration of glucose, in the absence or presence of 1 μM CsA, 250 μM N-acetyl cysteine (NAC) or 100 μM imeglimin. Cytotoxicity was evaluated by staining cells with Alexa Fluor-conjugated annexin V and PI. (a and b) Representative data. (c and d) Percentage of dead cells (i.e., cells positive for annexin V or PI) in five different experiments. Results are mean±S.E.M.; # P<0.01, *P<0.05 versus control cells, paired Student’s t-test.[2]. Detaille D, et al. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. Cell Death Discov. 2016 Jan 18;2:15072.
  • Effect of Imeglimin on cytochrome c distribution. HMEC-1 cells incubated in the presence or absence of Imeglimin were exposed to tBH or to hyperglycemic conditions as described in Figure 1. After 24 or 48 h (for tBH treatment and hyperglycemia, respectively), immunostaining was performed with specific anti-cytochrome c antibody. Representative data of five different experiments. Scale bar: 40 μm.[2]. Detaille D, et al. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. Cell Death Discov. 2016 Jan 18;2:15072.
  • Effects of Imeglimin on the Ca2+ retention capacity of digitonin-permeabilized HMEC-1 cells. (a) The incubation medium contained 250 mM sucrose, 1 mM Pi, 10 mM Tris-MOPS, 0.25 μM Calcium Green-5N, 50 μg/ml digitonin and either 5 mM succinate or 5 mM glutamate plus 2.5 mM malate. The final volume was 1 ml (pH 7.35) at 25 °C. Experiments were started by the addition of 107 HMEC-1 cells. Where indicated, 12.5 μM Ca2+ pulses were added (arrows). Panel (b) represents cumulative data of five different experiments performed as described in the panel (a) after preincubation with CsA (1 μM for 30 min) or Imeglimin (100 μM for 24 h). Results are mean±S.E.M.; # P<0.01; *P<0.05 versus control cells, paired Student’s t-test.[2]. Detaille D, et al. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. Cell Death Discov. 2016 Jan 18;2:15072.
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