| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Target: DPP-4 (dipeptidyl peptidase IV, also known as CD26). K-579 is a slow-binding, reversible inhibitor of DPP-4, a serine protease that rapidly degrades incretin hormones, including GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). DPP-4 inhibition increases the half-life and bioactivity of incretins, resulting in enhanced glucose-dependent insulin secretion, suppression of glucagon release, and improved glycemic control.
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| ln Vitro |
In vitro, K-579 inhibits DPP-4 activity with IC50 values of 3 nM (rat), 5 nM (human), 8 nM (monkey), and 8 nM (canine). It is a slow-binding inhibitor, showing time-dependent inhibition. It has high selectivity for DPP-4 over other proteases (DPP-8, DPP-9, FAP). No direct cytotoxicity is reported at therapeutic concentrations.
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| ln Vivo |
In vivo, K-579 is a long-acting hypoglycemic agent in animal models of type 2 diabetes. In rodents, oral administration of K-579 (1-30 mg/kg) reduces blood glucose levels, increases plasma GLP-1 and GIP levels, and improves glucose tolerance in oral glucose tolerance tests (OGTT). It also shows efficacy in diabetic db/db mice and Zucker fatty rats, reducing fasting blood glucose and HbA1c levels in subchronic studies.
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| Enzyme Assay |
For cell-free DPP-4 enzyme inhibition assays: recombinant human DPP-4 enzyme (50-100 ng) is incubated with varying concentrations of K-579 (0-100 nM) and a fluorogenic substrate (e.g., Gly-Pro-AMC, H-Gly-Pro-7-amido-4-methylcoumarin) in 100 uL assay buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl) for 30-60 min at 37degC. The reaction is stopped by adding 100 uL of 1 M sodium acetate (pH 4.2). Fluorescence is measured at excitation 380 nm and emission 460 nm. IC50 values are calculated from dose-response curves (5 nM for human).
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| Cell Assay |
For cell-based assays: Caco-2 cells (human intestinal epithelial cells that express DPP-4) are seeded in 96-well plates and treated with K-579 (0-100 nM) for 1-2 h. Cells are lysed, and cell lysates are incubated with fluorogenic DPP-4 substrate (Gly-Pro-AMC) for 30 min at 37degC. Fluorescence is measured to assess cellular DPP-4 activity. Alternatively, DPP-4 activity in serum or plasma from treated animals is measured by incubating with substrate and reading fluorescence. No direct cell viability effects are reported.
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| Animal Protocol |
For in vivo animal studies: male db/db mice (aged 8-12 weeks, fasting blood glucose >200 mg/dL) are orally administered K-579 (1-30 mg/kg) once daily for 4-8 weeks. Blood glucose levels are measured weekly from tail vein. OGTT is performed at week 2 and 4: blood glucose is measured at 0, 15, 30, 60, 90, 120 min after oral glucose administration (2 g/kg). Plasma GLP-1 and GIP levels are measured by ELISA. HbA1c is measured at study end. Pancreatic insulin content and beta-cell mass are assessed by histology and immunohistochemistry.
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| ADME/Pharmacokinetics |
PK properties of K-579: In rodents, after oral administration (1-10 mg/kg), Tmax is 1-2 h, plasma half-life is 4-8 h (suitable for once-daily dosing), and oral bioavailability is high (>70%). Volume of distribution is moderate, and plasma protein binding is moderate (∼80%). Metabolism is primarily by CYP3A4-mediated oxidation. The compound is excreted in urine and feces. Slow-binding kinetics contribute to its long-lasting action despite a moderate plasma half-life.
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| Toxicity/Toxicokinetics |
Toxicity profile of K-579: No significant toxicity has been reported in animal studies at therapeutic doses. DPP-4 inhibitors in general have a favorable safety profile, with mild gastrointestinal effects (nausea, diarrhea) and rare cases of pancreatitis. No acute toxicity or LD50 studies have been published. The compound is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
K-579 is a research compound not yet approved for clinical use (unlike other DPP-4 inhibitors such as sitagliptin, vildagliptin, saxagliptin). It is a valuable tool compound for studying DPP-4 biology, the incretin system, and type 2 diabetes. It is a cyanopyrrolidine DPP-4 inhibitor structurally related to vildagliptin. It can be used as a reference standard in bioanalytical method development for DPP-4 inhibitors.
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| Molecular Formula |
C17H24N6O
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|---|---|
| Molecular Weight |
328.4121
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| Exact Mass |
328.201
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| CAS # |
440100-64-1
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| PubChem CID |
9818824
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.333
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
487
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1(CCN(CC1)C2=NC=CC=N2)NCC(=O)N3CCC[C@H]3C#N
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| InChi Key |
JERPHRNGJBSFAP-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C17H24N6O/c1-17(21-13-15(24)23-9-2-4-14(23)12-18)5-10-22(11-6-17)16-19-7-3-8-20-16/h3,7-8,14,21H,2,4-6,9-11,13H2,1H3/t14-/m0/s1
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| Chemical Name |
(2S)-1-[2-[(4-methyl-1-pyrimidin-2-ylpiperidin-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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 : PEG300 ：Tween 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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0450 mL | 15.2249 mL | 30.4497 mL | |
| 5 mM | 0.6090 mL | 3.0450 mL | 6.0899 mL | |
| 10 mM | 0.3045 mL | 1.5225 mL | 3.0450 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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.
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