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| 500mg |
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Purity: ≥98%
Cetilistat (previously known as ATL-962) is a novel inhibitor of pancreatic and gastrointestinal lipases. It has the potential to treat obesity in both diabetic and non-diabetic patients. It is a highly lipophilic benzoxazinone analog with good PK, safety and tolerability profiles in vivo. Cetilistat acts by inhibiting pancreatic lipase which is an enzyme that breaks down triglycerides in the intestine. Triglycerides from the diet can not be hydrolyzed into the absorbable free fatty acids without this lipase enzyme and are excreted undigested.
| Targets |
The target of Cetilistat (ATL-962) is pancreatic lipase. It inhibits rat pancreatic lipase with an IC₅₀ of 54.8 nmol/l and human pancreatic lipase with an IC₅₀ of 5.95 nmol/l, showing 9.2 times higher potency against human pancreatic lipase than rat pancreatic lipase[1]
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| ln Vitro |
Rat pancreatic lipase activity is inhibited by cetilistat, with an IC50 of 54.8 nM. Moreover, cetilistat is 9.2 times more powerful than rat pancreatic lipase at inhibiting human pancreatic lipase activity, with an IC50 of 5.95 nM[1].
The in vitro activity of Cetilistat (ATL-962) is mainly reflected in its inhibitory effect on pancreatic lipase. Experiments showed that Cetilistat (ATL-962) could inhibit the activity of rat pancreatic lipase with an IC₅₀ value of 54.8 nmol/l, and also inhibit the activity of human pancreatic lipase with a lower IC₅₀ value of 5.95 nmol/l. This indicates that Cetilistat (ATL-962) has a strong inhibitory effect on pancreatic lipase in vitro, and its inhibitory effect on human pancreatic lipase is significantly stronger than that on rat pancreatic lipase[1] |
| ln Vivo |
In male SD rats, cetilistat (3, 10, 30, or 100 mg/kg) inhibits pancreatic lipase activity, reducing intestinal fat absorption[1]. By decreasing intestinal fat absorption, cetilistat (4.9, 14.9, or 50.7 mg/kg; mixed into powdered high-fat food; thrice a day; for three weeks) has anti-obesity and antihyperlipidemic effects on DIO F344 rats[1].
1. Effect on plasma triglyceride (TG) concentration in Sprague-Dawley rats: Cetilistat (ATL-962) was orally administered to Sprague-Dawley rats simultaneously with fat emulsion at doses of 3, 10, 30, and 100 mg/kg. The results showed that Cetilistat (ATL-962) could reduce the elevation of plasma triglyceride concentration caused by oral fat loading in a dose-dependent manner, indicating that it can reduce intestinal fat absorption in rats[1] 2. Effect on diet-induced obesity (DIO) F344 rats: Cetilistat (ATL-962) was administered to DIO F344 rats as a food admixture in a high-fat diet at doses of 4.9, 14.9, and 50.7 mg/kg/day for three weeks. It was found that the content of triglyceride and nonesterified fatty acid in feces increased drastically in a dose-dependent manner, suggesting that Cetilistat (ATL-962) promotes the breakdown and excretion of intestinal fat. Meanwhile, body weight (BW) gain and white adipose tissue (WAT) weight of the rats were reduced in a dose-dependent manner. In addition, plasma levels of leptin, triglyceride (TG), and total cholesterol (TC) were also reduced, and there were no reports of oily stools[1] |
| Enzyme Assay |
The enzyme activity assay for Cetilistat (ATL-962) mainly focuses on the determination of its inhibitory effect on pancreatic lipase. The specific process is as follows: First, prepare the reaction system containing rat or human pancreatic lipase and the corresponding substrate. Then, add different concentrations of Cetilistat (ATL-962) to the reaction system, and set up a control group without Cetilistat (ATL-962). After incubating the reaction system under appropriate temperature and time conditions, detect the change of substrate or product concentration in the system by relevant detection methods (such as spectrophotometry) to reflect the activity of pancreatic lipase. Finally, calculate the IC₅₀ value of Cetilistat (ATL-962) for inhibiting rat and human pancreatic lipase according to the changes in enzyme activity at different drug concentrations[1]
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| Animal Protocol |
Animal/Disease Models: Fifty male SD rats (eight weeks of age)[1]
Doses: 3, 10 , 30, or 100 mg/kg Route of Administration: Orally administered; prepared in 0.5 % methylcellulose (MC) suspension Experimental Results: Dose-dependently decreased AUC 0-6 h of plasma triglyceride induced by oral loading of Intrafat 20%. The effect was statistically significant at 3 mg/kg, reaching 45% reduction, while an almost 90 % reduction was achieved at 100 mg/kg. Animal/Disease Models: Male diet-induced obesity (DIO) F344 rats (five weeks of age)[1] Doses: 4.9 , 14.9, or 50.7 mg/kg Route of Administration: Administered as food admixture in a high-fat diet; one time/day; for three weeks Experimental Results: Dramatically and dose-dependently decreased body weight gain compared with control. 1. Animal experiment on Sprague-Dawley rats (to observe the effect on plasma triglyceride concentration): Select Sprague-Dawley rats as experimental animals. Cetilistat (ATL-962) is orally administered to the rats simultaneously with fat emulsion. The doses of Cetilistat (ATL-962) are set as 3, 10, 30, and 100 mg/kg. Before and after oral fat loading, collect blood samples from the rats to measure the plasma triglyceride (TG) concentration, so as to evaluate the effect of Cetilistat (ATL-962) on reducing the elevation of plasma triglyceride caused by fat loading[1] 2. Animal experiment on DIO F344 rats (to observe the anti-obesity and lipid-lowering effects): Use diet-induced obesity (DIO) F344 rats as experimental models. Cetilistat (ATL-962) is mixed into a high-fat diet as a food admixture and administered to the rats. The doses are 4.9, 14.9, and 50.7 mg/kg/day, and the administration lasts for three weeks. During the experiment, regularly record the body weight of the rats. After the experiment, collect feces to detect the content of triglyceride and nonesterified fatty acid, dissect the rats to take white adipose tissue (WAT) and weigh it, and collect blood samples to measure plasma levels of leptin, triglyceride (TG), and total cholesterol (TC)[1] |
| References | |
| Additional Infomation |
Cetilistat is a benzoxazine antibiotic. Developed by Alizyme, silicone is a novel pancreatic lipase inhibitor used to treat obesity and related comorbidities, including type 2 diabetes. Drug Indications It has been studied for the treatment of obesity. Mechanism of Action Cetilistat is a gastrointestinal lipase inhibitor that blocks the digestion and absorption of fat, thereby reducing energy intake and achieving weight loss. Unlike most other anti-obesity drugs, it does not act on the brain to suppress appetite but rather through peripheral pathways. This compound is primarily found in the gastrointestinal tract and is not absorbed in large quantities by the body. Silicone (ATL-962) is a novel pancreatic lipase inhibitor. Pancreatic lipase is an important enzyme involved in the digestion and absorption of fat in the intestines. By inhibiting the activity of pancreatic lipase, silicone (ATL-962) can reduce the digestion and absorption of fat in the intestines, thereby reducing fat calorie intake and improving weight gain and lipid profile. The results of experiments in diet-induced obesity (DIO) rats (an animal model that mimics the most common type of obesity in humans) indicate that cillistat (ATL-962) has the potential to improve obesity and hyperlipidemia, laying the foundation for its further research and development in the fields of anti-obesity and lipid-lowering [1].
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| Molecular Formula |
C25H39NO3
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| Molecular Weight |
401.58
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| Exact Mass |
401.292
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| CAS # |
282526-98-1
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| Related CAS # |
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| PubChem CID |
9952916
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| Appearance |
White to off-white solid powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
509.7±43.0 °C at 760 mmHg
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| Melting Point |
74°C
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| Flash Point |
158.9±22.6 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.521
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| LogP |
9.93
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
29
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| Complexity |
477
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MVCQKIKWYUURMU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H39NO3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-19-28-25-26-23-18-17-21(2)20-22(23)24(27)29-25/h17-18,20H,3-16,19H2,1-2H3
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| Chemical Name |
2-hexadecoxy-6-methyl-3,1-benzoxazin-4-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4902 mL | 12.4508 mL | 24.9016 mL | |
| 5 mM | 0.4980 mL | 2.4902 mL | 4.9803 mL | |
| 10 mM | 0.2490 mL | 1.2451 mL | 2.4902 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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