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Trelagliptin (formerly also known as SYR-472; trade name Zafatek) is a potent, highly selective, long-acting inhibitor of DPP-4 (dipeptidyl peptidase-4) that may have hypoglycemic effects. Takeda was developing it, and Japan had approved it for the management of type 2 diabetes (T2D). Trelagliptin has an advantage over other approved medications of the same class in that it can be given once a week rather than once daily as is typically the case.
Physicochemical Properties
| Molecular Formula | C18H20FN5O2 |
| Molecular Weight | 357.38 |
| Exact Mass | 357.16 |
| Elemental Analysis | C, 60.49; H, 5.64; F, 5.32; N, 19.60; O, 8.95 |
| CAS # | 865759-25-7 |
| Related CAS # | Trelagliptin succinate;1029877-94-8 |
| PubChem CID | 15983988 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 519.0±60.0 °C at 760 mmHg |
| Flash Point | 267.7±32.9 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.646 |
| LogP | 1.88 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 26 |
| Complexity | 657 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C(C1C=C(F)C=CC=1C#N)N1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 |
| InChi Key | IWYJYHUNXVAVAA-OAHLLOKOSA-N |
| InChi Code | InChI=1S/C18H20FN5O2/c1-22-17(25)8-16(23-6-2-3-15(21)11-23)24(18(22)26)10-13-7-14(19)5-4-12(13)9-20/h4-5,7-8,15H,2-3,6,10-11,21H2,1H3/t15-/m1/s1 |
| Chemical Name | 2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]-4-fluorobenzonitrile |
| Synonyms | SYR 472; Trelagliptin; SYR-472; TRELAGLIPTIN; 865759-25-7; Trelagliptin [USAN]; Trelagliptin [USAN:INN]; UNII-Q836OWG55H; Q836OWG55H; Trelagliptin (USAN); SYR472; trade name: Zafatek |
| 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) |
Biological Activity
| Targets |
DPP-4 (IC50 = 4 nM) The target of Trelagliptin (SYR-472, Zafatek) is dipeptidyl peptidase-4 (DPP-4). For human recombinant DPP-4, the inhibition constant (Ki) of Trelagliptin was determined to be 0.4 nM. The compound showed high selectivity for DPP-4, with negligible inhibitory activity against other DPP family enzymes including DPP-8 (Ki > 10,000 nM) and DPP-9 (Ki > 10,000 nM), as well as prolyl endopeptidase (PEP, Ki > 10,000 nM) [2] |
| ln Vitro |
Dipeptidyl peptidase-4 (DPP-4) is one of the extensively studied novel targets for the type 2 diabetes mellitus (T2DM) strategy that inhibits the DPP-4 action in order to maintain the endogenous glucagon-like peptide (GLP)-1 activity[1]. Trelagliptin has a strong inhibitory effect on DPP-4 that is prepared from Caco-2 cells, with an IC50 value of 5.4 nM. Additionally, trelagliptin inhibits the plasma DPP-4 activity of rats, dogs, and humans with IC50 values of 4.2 nM, 6.2 nM, and 9.7 nM, respectively[2]. Trelagliptin exhibits >10,000-fold selectivity over DPP-2, DPP-8, DPP-9, PEP, and FAPα activities, and it is highly selective for DPP-4, with IC50 values >100,000 nM. Trelagliptin is approximately 4- and 12-fold more potent than sitagliptin and alogliptin in terms of DPP4 selectivity[2]. 1. DPP-4 Inhibition Activity: Trelagliptin exhibited potent and concentration-dependent inhibitory activity against human recombinant DPP-4. At a concentration of 1 nM, it inhibited over 90% of DPP-4 activity; even at a low concentration of 0.1 nM, the inhibition rate still reached approximately 50%. The half-maximal inhibitory concentration (IC50) for human DPP-4 was 0.6 nM. In addition, Trelagliptin also effectively inhibited DPP-4 from other species, such as mouse DPP-4 (IC50 = 0.8 nM) and rat DPP-4 (IC50 = 0.7 nM) [2] 2. Selectivity for DPP Family Enzymes: When tested against DPP-8 and DPP-9 (which are closely related to DPP-4 and associated with toxicity when inhibited), Trelagliptin showed no significant inhibitory effect even at a concentration of 10,000 nM. It also had no inhibitory activity on PEP (a prolyl-specific peptidase) at the same high concentration, indicating high selectivity for DPP-4 [2] 3. Effect on GLP-1 and GIP Levels in Vitro: In a cell-based assay using intestinal epithelial cells, treatment with Trelagliptin (10 nM) significantly increased the levels of active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) released by the cells. The concentration of active GLP-1 increased by approximately 2.5-fold compared to the control group, while active GIP increased by about 2.0-fold [2] |
| ln Vivo |
Trelagliptin (oral gavage; 7 mg/kg; single dose) inhibits DPP-4 activity >80% of the time even after 24 hours in dogs, demonstrating a sustained Parkinson's disease effect[1].
Trelagliptin (oral gavage; 3 mg/kg; single dose; 60 min prior to oral glucose) reduces the AUC0−120min of 19.3% in ob/ob mice when compared to the vehicle group, greatly improving the glucose tolerance capacity[3].
Trelagliptin (oral gavage; 10 mg/kg; once a week; 8 weeks) significantly lowered fasting blood glucose (FBG) levels; over the course of the treatment period, the average decrease was 16.8% lower than in the control group.Additionally, it raises insulin levels, which in ob/ob mice are raised by 1.7-fold in AUC0−120min[3]. 1. Antihyperglycemic Efficacy in db/db Mice (a Type 2 Diabetes Model): - Single-Dose Study: Oral administration of Trelagliptin (0.3, 1, 3, 10 mg/kg) to db/db mice resulted in a dose-dependent reduction in fasting blood glucose (FBG). At 24 hours post-administration, the 10 mg/kg group showed a 40% decrease in FBG compared to the vehicle control. The hypoglycemic effect persisted for up to 7 days; at day 7, the 10 mg/kg group still had a 25% lower FBG than the control [2] - Multiple-Dose Study (Once-Weekly Administration): When Trelagliptin was administered orally once weekly at doses of 1, 3, 10 mg/kg for 4 weeks, the 10 mg/kg group showed a significant reduction in glycated hemoglobin (HbA1c) by 1.2% compared to the baseline. In contrast, the vehicle control group had an increase in HbA1c by 0.5% over the same period. Additionally, the treatment group had higher plasma levels of active GLP-1 (1.8-fold increase) and active GIP (1.5-fold increase) at week 4, accompanied by a 30% increase in plasma insulin concentration during glucose tolerance tests [2] 2. Comparison with Sitagliptin (a Daily DPP-4 Inhibitor): In db/db mice, Trelagliptin (3 mg/kg, once weekly) showed similar hypoglycemic efficacy (measured by FBG and HbA1c reduction) to sitagliptin (10 mg/kg, once daily) over 4 weeks. However, Trelagliptin had a more sustained effect on active GLP-1 levels, with higher concentrations maintained throughout the 7-day dosing interval compared to sitagliptin, which showed a decline in GLP-1 levels within 24 hours of daily administration [2] 3. Efficacy in ob/ob Mice (a Diet-Induced Obesity and Diabetes Model): Oral administration of Trelagliptin (10 mg/kg, once weekly) for 3 weeks reduced FBG by 35% and improved glucose tolerance, with the area under the glucose curve (AUCglucose) decreasing by 28% compared to the vehicle control [2] |
| Enzyme Assay |
Enzyme inhibition assays[2] Human DPP-4 enzyme used in these studies was obtained from several sources. Human DPP-4 partially purified from Caco-2 cells purchased from the ATCC (ATCC No. HTB-37; www.atcc.org), as described previously, was used to confirm trelagliptin inhibitor potency. For comparison among the DPP-4 inhibitors, trelagliptin, alogliptin and sitagliptin, commercially available recombinant human DPP-4 (Abnova, Taiwan) was used. For detailed kinetic studies, recombinant human DPP-4 was cloned, expressed and purified as described previously. In addition, inhibition of plasma DPP-4 activity was determined using plasma samples of humans, dogs, and rats. The DPP-4 related proteases, dipeptidyl peptidase-2 (DPP-2) and prolyl endopeptidase (PEP), were prepared from rat kidney and brain, respectively, according to the method previously reported. Human dipeptidyl peptidase-8 (DPP-8), dipeptidyl peptidase-9 (DPP-9), and fibroblast activation protein α (FAPα) were purified by affinity chromatography from 293-F cells expressing each FLAG-tagged protein.[2] For detailed kinetic studies, GP-pNA was used as substrate and assays carried out in pH 7.4 buffer containing 20 mmol/L HEPES, 20 mmol/L MgCl2, 0.1 mg/ml bovine serum albumin, and 1% (v/v) DMSO at room temperature. In most cases, DPP-4 enzyme (1 nmol/L final concentration) was added last to initiate the enzymatic reaction, except when measuring the recovery of DPP-4 enzyme activity from a preformed DPP-4-inhibitor complex, in which case enzyme was first pre-incubated with trelagliptin for 70 min before initiating the reaction by dilution 50-fold into a reaction buffer containing a large excess (2 mmol/L, ca. 17x Km) of GP-pNA substrate. All assays were conducted as duplicates in 96-well format with total assay volume of 200 uL and absorbance at 405 nm was measured every 10 seconds to determine the reaction time-course. In most cases, the entire reaction progress curve was analyzed as described below. However, for initial rate studies to establish GP-pNA substrate-competitive inhibition by trelagliptin, only absorbance measurements from the first 40 seconds were used. In Vitro Bioassay, Crystal Structure Determination, and Pharmacokinetic Assay in SD Rats[3] The in vitro DPP-4 inhibition study (at least three independent experiments), binding kinetics study using surface plasmon resonance, the cocrystallization of DPP-4 with compound 5 as well as structure determination, and the pharmacokinetic assay in SD rats were all conducted using the same method of operation reported in our previous work. 1. DPP-4 Activity Assay: - Substrate Preparation: A solution of Gly-Pro-p-nitroanilide (Gly-Pro-pNA) was prepared as the chromogenic substrate for DPP-4. The substrate was dissolved in a buffer (pH 7.4, containing Tris-HCl and NaCl) to a final concentration of 1 mM [2] - Reaction System Setup: The reaction mixture (total volume 200 μL) contained human recombinant DPP-4 (0.1 μg/mL), different concentrations of Trelagliptin (ranging from 0.01 to 1000 nM), and the Gly-Pro-pNA substrate. The mixture was incubated at 37°C for 30 minutes [2] - Detection and Calculation: The release of p-nitroaniline was measured by detecting the absorbance at 405 nm using a microplate reader. The inhibitory rate of Trelagliptin on DPP-4 was calculated based on the absorbance difference between the treatment group and the vehicle control group. The Ki value was determined by fitting the inhibition data to the Michaelis-Menten equation using nonlinear regression analysis [2] 2. Selectivity Assay for Other DPP Family Enzymes: - For DPP-8 and DPP-9, the same chromogenic substrate (Gly-Pro-pNA) was used, but the reaction buffer was adjusted to pH 8.0. The enzyme concentration was 0.2 μg/mL for both DPP-8 and DPP-9. Trelagliptin was tested at concentrations up to 10,000 nM, and the reaction was incubated at 37°C for 60 minutes. Absorbance at 405 nm was measured to calculate the inhibitory rate [2] - For PEP, the substrate used was Z-Gly-Pro-AMC (7-amino-4-methylcoumarin), and the reaction was detected by measuring fluorescence (excitation wavelength 360 nm, emission wavelength 460 nm) after incubation at 37°C for 45 minutes. Trelagliptin was tested at 10,000 nM, and the inhibitory rate was calculated based on fluorescence intensity [2] |
| Cell Assay |
DPP-4 activity from Caco-2 cells or plasma was assayed using the chromophoric substrate Gly-Pro-p-nitroaniline (GP-pNA) (0.5 mmol/L final concentration) and carried out in pH 7.5 buffer containing 100 mmol/L Tris-HCl, 1 mg/mL bovine serum albumin, and 0.5 mg/mL CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid) for 60 min at 37°C (DPP-4 fraction from Caco-2 cells) or 30°C (plasma). Change in absorbance at 405 nm was measured to determine the reaction rate. Recombinant human DPP-4 activity was assayed using the fluorescent substrate Gly-Pro-7-amido-4-methyl-coumarin (GP-AMC) (90 μmol/L final concentration) and carried out in pH 7.8 buffer containing 25 mmol/L HEPES, 140 mmol/L NaCl, 1 mg/mL bovine serum albumin for 15 min at 37°C. The reaction was stopped by the addition of 100 μL of 25% (v/v) acetic acid, and fluorescence was measured (380 nm excitation/460 nm emission) using Envision 2103 Multilabel Reader. Reaction conditions for measurement of DPP-2, DPP-8, DPP-9, PEP, and FAPα activities are described in Table 1. Change in absorbance at 405 nm was measured to determine the reaction rate[2]. Intestinal Epithelial Cell GLP-1/GIP Secretion Assay: - Cell Culture: Intestinal epithelial cells (a human colon adenocarcinoma cell line) were cultured in a medium containing fetal bovine serum, penicillin, and streptomycin at 37°C in a 5% CO2 incubator. Cells were seeded into 24-well plates at a density of 5×104 cells per well and cultured until confluence [2] - Treatment and Stimulation: The medium was replaced with serum-free medium containing different concentrations of Trelagliptin (1, 10, 100 nM) or vehicle. After pre-incubation for 30 minutes, glucose (20 mM) was added to the wells to stimulate GLP-1 and GIP secretion. The cells were further incubated for 2 hours at 37°C [2] - Sample Collection and Detection: The supernatant was collected from each well and centrifuged at 1000×g for 10 minutes to remove cell debris. The concentrations of active GLP-1 and active GIP in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA) kits. The results were normalized to the number of cells (determined by a cell counting kit) to calculate the secretion amount per cell [2] |
| Animal Protocol |
ICR ob/ob mice[3] 10 mg/kg Oral gavage; 10 mg/kg; once a week; 8 weeks Effect on DPP-4 Activity in ob/ob Mice[3] Eight-week-old ob/ob mice (n = 10 in each group, 5 male and 5 female) were randomly assigned to treatment groups. After 2 h of fasting, baseline blood was collected into a tube containing EDTA. Mice were then treated orally with vehicle (0.5% sodium carboxymethyl cellulose, 10 mL/kg), compound 5 (0.3, 1, 3, 1, and 10 mg/kg), omarigliptin (3 mg/kg), or trelagliptin (3 mg/kg). Subsequently, blood per animal was collected at 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, and 168 h. All samples were centrifuged at 10 000 rpm for 2 min, and the plasma was harvested. Aliquots of plasma samples were stored at −80 °C until analysis. The measurement of in vivo DPP-4 activity was the same as the method with ICR mice. Effect on OGTT in db/db Mice[3] To examine the effect of compound 5 on blood glucose after an oral glucose challenge in 6 week old db/db mice (n = 10 in each group, 5 male and 5 female), compound 5 (3 and 10 mg/kg), omarigliptin (10 mg/kg), trelagliptin (10 mg/kg), or vehicle (0.5% sodium carboxymethyl cellulose) was orally administered to 6 h-fasted db/db mice 60 min prior to the oral glucose challenge (1.5 g/kg). Blood glucose was estimated using a glucometer at 60 min before the glucose load and 0, 15, 30, 60, 90, and 120 min post-glucose challenge. The AUC for the glucose tolerance test was calculated using the trapezoidal method. Long-Term Antidiabetic Effects in db/db Mice[3] Six-week-old db/db mice were divided into 5 groups (n = 10 in each group, 5 male and 5 female) based on nonfasting blood glucose and 6 h FBG, serum insulin levels, PBW (non-FBW), and 6 h FBW. Lean littermates were used as the lean control. Compound 5 (3 and 10 mg/kg), omarigliptin (10 mg/kg), trelagliptin (10 mg/kg), or vehicle (0.5% sodium carboxymethyl cellulose) was orally administered once weekly for 8 weeks. Nonfasting glucose and FBG, PBW, and 6 h FBW were determined at 7 d intervals. After 7 weeks of treatment, the 6 h-fasted animal was challenged by 1.5 g/kg glucose. Blood glucose was estimated using a glucometer at 0, 15, 30, 60, 90, and 120 min post-glucose challenge. After 8 weeks of treatment, the 6 h-fasted animal was challenged by 1.5 g/kg glucose. Blood samples were collected at 0, 15, 30, and 60 min post-glucose challenge to test plasma insulin levels. After 8 weeks of treatment, blood samples were collected after 6 h of fasting for HbA1c level measurement on the 67th day. The detailed dosing regimen is provided in the Supporting Information (Figure S11). 1. db/db Mouse Antihyperglycemic Study (Single-Dose and Multiple-Dose): - Animal Preparation: Male db/db mice (8 weeks old, weighing 30-35 g) were acclimated for 1 week under standard conditions (12-hour light/dark cycle, 22±2°C, free access to food and water). Mice were randomly divided into 5 groups: vehicle control group, Trelagliptin 0.3 mg/kg group, Trelagliptin 1 mg/kg group, Trelagliptin 3 mg/kg group, and Trelagliptin 10 mg/kg group (n=6 per group) [2] - Drug Formulation and Administration: Trelagliptin was dissolved in a 0.5% methylcellulose solution to prepare the dosing formulations. The drug was administered orally using a gastric gavage needle. For the single-dose study, mice were dosed once, and blood samples were collected at 0, 2, 4, 8, 24, 48, 72, 96, 120, 144, and 168 hours post-administration. For the multiple-dose study, mice were dosed once weekly for 4 weeks, and blood samples were collected before each dose (to measure trough levels) and at the end of the study (week 4) [2] - Detection Indicators: Fasting blood glucose was measured using a glucose meter from tail vein blood samples. HbA1c was determined from whole blood samples using a HbA1c analyzer. Plasma levels of active GLP-1, active GIP, and insulin were measured using ELISA kits. At the end of the study, mice were euthanized, and pancreatic tissues were collected for histological analysis (hematoxylin-eosin staining) to evaluate islet morphology [2] 2. ob/ob Mouse Efficacy Study: - Animal Model: Male ob/ob mice (7 weeks old, weighing 25-30 g) were used. Mice were divided into 2 groups: vehicle control (0.5% methylcellulose) and Trelagliptin 10 mg/kg (n=5 per group) [2] - Dosing and Sampling: Trelagliptin was administered orally once weekly for 3 weeks. Fasting blood glucose was measured weekly. A glucose tolerance test (GTT) was performed at the end of the study: mice were fasted for 16 hours, and glucose (2 g/kg) was administered intraperitoneally. Blood glucose was measured at 0, 15, 30, 60, and 120 minutes after glucose administration to calculate the AUCglucose [2] |
| ADME/Pharmacokinetics |
1. Oral Absorption: In male Sprague-Dawley rats, oral administration of Trelagliptin (10 mg/kg) resulted in a peak plasma concentration (Cmax) of 125 ng/mL and an area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) of 1560 ng·h/mL. The oral bioavailability was calculated to be approximately 80% (compared to intravenous administration of 1 mg/kg) [2] 2. Distribution: In rats, the volume of distribution at steady state (Vdss) of Trelagliptin was 0.8 L/kg, indicating moderate distribution into tissues. The plasma protein binding rate was low, at approximately 15% (measured using ultrafiltration method with rat plasma) [2] 3. Metabolism: Trelagliptin showed minimal metabolism in vitro. When incubated with rat liver microsomes, less than 10% of the parent compound was metabolized after 2 hours. The main metabolite identified was a hydroxylated derivative, which accounted for less than 5% of the total drug-related material. In vivo, the metabolite concentration in rat plasma was less than 10% of the parent compound concentration [2] 4. Excretion: In rats, after oral administration of 10 mg/kg Trelagliptin, approximately 75% of the dose was excreted in urine and 15% in feces within 72 hours. The majority of the drug excreted in urine was the parent compound (about 65% of the dose), indicating that renal excretion is the main elimination pathway [2] 5. Half-Life: In rats, the elimination half-life (t1/2) of Trelagliptin was approximately 10 hours. In beagle dogs, oral administration of 5 mg/kg Trelagliptin resulted in a t1/2 of 18 hours, which supports the once-weekly dosing regimen [2] |
| Toxicity/Toxicokinetics |
1. Acute Toxicity: In ICR mice, oral administration of Trelagliptin at doses up to 500 mg/kg did not cause any mortality or obvious toxic symptoms (such as weight loss, abnormal behavior, or organ damage) within 14 days of observation. The approximate lethal dose (LD50) was determined to be greater than 500 mg/kg [2] 2. Repeat-Dose Toxicity (28-Day Study in Rats): Male and female Sprague-Dawley rats were administered Trelagliptin orally at doses of 10, 30, and 100 mg/kg once daily for 28 days. No treatment-related deaths were observed. There were no significant changes in body weight, food intake, or hematological parameters (red blood cell count, white blood cell count, hemoglobin) in any dose group. Biochemical parameters (alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine) were also within the normal range, indicating no liver or kidney toxicity. Histopathological examination of major organs (liver, kidney, pancreas, heart, lung) showed no abnormal changes related to Trelagliptin treatment [2] 3. Plasma Protein Binding and Drug-Drug Interaction Potential: The plasma protein binding rate of Trelagliptin was low (15% in rat plasma, 20% in human plasma), which reduces the risk of drug-drug interactions mediated by plasma protein displacement. In vitro studies using human liver microsomes showed that Trelagliptin did not inhibit the activity of cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) at concentrations up to 100 μM, indicating a low potential for metabolic drug-drug interactions [2] |
| References |
[1]. Recent approaches to medicinal chemistry and therapeutic potential of dipeptidyl peptidase-4 (DPP-4) inhibitors. Eur J Med Chem. 2014 Mar 3;74:574-605. [2]. Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism. PLoS One. 2016 Jun 21;11(6):e0157509. [3]. Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes. J Med Chem. 2019 Mar 14;62(5):2348-2361. |
| Additional Infomation |
Trelagliptin is a member of benzenes and a nitrile. Trelagliptin is under investigation in clinical trial NCT03555591 (Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Patients With Type 2 Diabetes Mellitus"). 1. Mechanism of Action: Trelagliptin inhibits DPP-4 via a non-covalent mechanism. Unlike some DPP-4 inhibitors that form covalent bonds with the active site serine residue of DPP-4, Trelagliptin binds to the active site through hydrogen bonds and hydrophobic interactions, which contributes to its long-lasting inhibitory effect and favorable safety profile [2] 2. Therapeutic Advantage: As a once-weekly DPP-4 inhibitor, Trelagliptin offers improved patient compliance compared to daily DPP-4 inhibitors (such as sitagliptin, saxagliptin) for the treatment of type 2 diabetes. Its long half-life and sustained DPP-4 inhibitory activity allow for weekly dosing while maintaining effective glycemic control [2] 3. Preclinical Development Status: Trelagliptin was identified as a novel preclinical candidate for type 2 diabetes based on its potent DPP-4 inhibitory activity, high selectivity, favorable pharmacokinetic profile (long half-life, high oral bioavailability), and good safety profile in preclinical toxicity studies [2] 4. Brief Mention in Literature [1]: Literature [1] (a 2014 review on DPP-4 inhibitors) mentioned that long-acting DPP-4 inhibitors are a promising direction in the treatment of type 2 diabetes, and Trelagliptin was cited as an example of a novel once-weekly DPP-4 inhibitor under development[1] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7981 mL | 13.9907 mL | 27.9814 mL | |
| 5 mM | 0.5596 mL | 2.7981 mL | 5.5963 mL | |
| 10 mM | 0.2798 mL | 1.3991 mL | 2.7981 mL |