GLP-1 receptor
Semaglutide is derivatized at lysine 26 and differs from human GLP-1 in two amino acid substitutions (Aib⁸, Arg³⁴). Semaglutide has an affinity for GLP-1R of 0.38±0.06 nM[1]. A GLP-1 analogue that is 94% sequence similar to human GLP-1 is semaglutide [3].

Semaglutide is derivatized at lysine 26 and differs from human GLP-1 in two amino acid substitutions (Aib⁸, Arg³⁴). Semaglutide has an affinity for GLP-1R of 0.38±0.06 nM[1]. A GLP-1 analogue that is 94% sequence similar to human GLP-1 is semaglutide [3].

Semaglutide has an MRT of 63.6 hours after s.c. dosing to mini-pigs and a plasma half-life of 46 hours in mini-pigs after intravenous administration[1]. Motor impairments caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are ameliorated by semaglutide. Semaglutide also protects dopaminergic neurons in the substantia nigra and striatum by rescuing the decrease in tyrosine hydroxylase (TH) levels, reducing lipid peroxidation, alleviating inflammation, inhibiting the apoptosis pathway, and increasing the expression of autophagy-related proteins. Furthermore, semaglutide, a long-acting GLP-1 analogue, outperforms liraglutide in the majority of parameters[2]. Semaglutide reduces body weight and blood glucose by promoting the release of insulin[3].

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In patients with type 2 diabetes at high cardiovascular risk, once-weekly subcutaneous semaglutide (0.5 mg or 1.0 mg) significantly reduced the risk of the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) compared to placebo over a median 2.1 years of treatment. The hazard ratio was 0.74 (95% CI, 0.58 to 0.95; P<0.001 for noninferiority; P=0.02 for superiority). The number needed to treat (NNT) to prevent one primary outcome event over 24 months was 45. [1]
The reduction in the primary outcome was driven by a significant 39% reduction in nonfatal stroke (HR 0.61; 95% CI, 0.38 to 0.99; P=0.04) and a non-significant 26% reduction in nonfatal myocardial infarction (HR 0.74; 95% CI, 0.51 to 1.08; P=0.12). The rate of cardiovascular death was similar between groups (HR 0.98; 95% CI, 0.65 to 1.48; P=0.92). [1]
Semaglutide treatment also resulted in a lower risk of new or worsening nephropathy (HR 0.64; 95% CI, 0.46 to 0.88; P=0.005) but a higher risk of diabetic retinopathy complications (HR 1.76; 95% CI, 1.11 to 2.78; P=0.02) compared to placebo. [1]
Significant improvements in glycemic control and body weight were observed. At week 104, glycated hemoglobin decreased by 1.1% (0.5 mg) and 1.4% (1.0 mg) from a baseline of 8.7% with semaglutide, versus 0.4% with placebo. Body weight decreased by 3.6 kg (0.5 mg) and 4.9 kg (1.0 mg) with semaglutide, versus 0.5-0.7 kg with placebo. [1]

HEK293‐SNAP‐GLP‐1R cells were labelled in suspension with SNAP‐Lumi4‐Tb (40 nM, Cisbio, Codelet, France) for 1 hour at room temperature in complete medium. After washing and resuspension in hanks' balanced salt solution containing 0.1% bovine serum albumin and metabolic inhibitors (20 mmol/L 2‐deoxygucose and 10 mmol/L NaN3) to prevent GLP‐1R internalization, binding experiments were performed by time‐resolved förster resonance energy transfer (FRET) using exendin (9‐39) with fluorescein isothiocyanate (FITC) installed at position K12 as previously described.[4]

Semaglutide activates the GLP-1 receptor in pancreatic beta cells leading to glucose-dependent insulin release. It also decreases glucagon secretion, slows gastric emptying, and promotes satiety.

Mice: Male C57BL/6 mice 10 weeks old (20-25 g) are used throughout the study. Six groups of mice are randomly assigned (n = 12 per group). The treatments were as follows: (i) saline alone was given to the control group; (ii) NN-2211 group received saline and NN-2211 (25 nmol/kg ip. once daily for 7 days); (iii) Semaglutide group received saline and Semaglutide (25 nmol/kg ip. once daily for 7 days); (iv) MPTP group received MPTP alone (once daily 20 mg/kg ip. for 7 days); (v) MPTP (once daily 20 mg/kg ip. for 7 days) was immediately followed by NN-2211 treated group (25 nmol/kg ip. once daily for 7 days). (vi) MPTP (20 mg/kg i.p. once daily for 7 days), which was immediately followed by the group treated with semaglutide (25 nmol/kg i.p. once daily for 7 days). Measure behavioral changes, neuronal damage, inflammatory markers, and other biomarkers at the conclusion of drug treatments. [2]

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Male C57BL/6 mice (10 weeks old) were used. Parkinson's disease was modeled by intraperitoneal (i.p.) injection of MPTP (20 mg/kg) once daily for 7 days.
For the treatment groups, semaglutide was dissolved in saline and administered via i.p. injection at a dose of 25 nmol/kg, once daily for 7 days. The treatment started immediately after the daily MPTP injection.
Behavioral assessments (open-field test, rotarod test, footprint test) were conducted on the 8th day after the start of MPTP injections.
On the 9th day, mice were euthanized. Brain tissues (substantia nigra and striatum) were collected for subsequent immunohistochemistry and western blot analysis. For immunohistochemistry, brains were perfused with saline and fixed with paraformaldehyde. For western blot, brain regions were dissected and frozen at -80°C.[2]

Absorption: In a clinical trial, semaglutide's Cmax was 10.9 nmol/L, AUC was 3123.4 nmol·h/L, and Tmax was 56 h, achieved within 1-3 days. Absolute bioavailability was 89%. Steady-state concentrations of oral tablets were reached within 4-5 weeks. The mean steady-state concentration of semaglutide refers to the mean steady-state concentration after administration of a dose from 0.5 mg to 1 mg, ranging from 16 nmol/L to 30 nmol/L. Elimination pathway: The drug is primarily cleared by the kidneys and can be excreted in urine and feces. The primary elimination route is urine, accounting for approximately 53% of the ingested radiolabeled dose, followed by feces, accounting for approximately 18.6%. A small amount (3.2%) is excreted via exhalation. Hepatic impairment does not appear to affect the drug's clearance, and no dose adjustment is required for patients with impaired hepatic function. Volume of distribution: Semaglutide has a volume of distribution of 8 to 9.4 liters. It crosses the rat placenta.
Clearance: According to a clinical study, the clearance of semaglutide is 0.039 L/h. The FDA label indicates that the clearance of semaglutide in patients with type 2 diabetes is approximately 0.05 L/h.

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Metabolism/Metabolites: Semaglutide is cleaved at the peptide backbone, followed by β-oxidation of the fatty acid chain. Naturally occurring GLP-1 is rapidly metabolized by dipeptidyl peptidase-4 (DPP-4) and other enzymes widely present in human tissues. Chemical modifications make semaglutide less susceptible to degradation by gastrointestinal DPP-4 enzymes. It is metabolized slowly and extensively, with approximately 83% of the administered dose present in plasma as the parent drug. Neuroendopeptidase (NEP) is another enzyme that metabolizes this drug. DPP-4 inactivates semaglutide by cleaving the N-terminal fragment, while NEP hydrolyzes peptide bonds. Six different semaglutide metabolites have been identified in human plasma. The major metabolite, P3, accounts for approximately 7.7% of the ingested dose. Biological half-life: One of the main characteristics of semaglutide is its long half-life of 168 hours. This long half-life is attributed to its binding to albumin. This reduces renal clearance and protects semaglutide from metabolic degradation.

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Semaglutide is a long-acting GLP-1 analog, administered subcutaneously once weekly for the treatment of type 2 diabetes. It is a modified version of liraglutide designed to resist protease degradation, thereby prolonging its biological half-life. Specific pharmacokinetic parameters (e.g., half-life, Cmax, AUC) were not provided in this study. [2]

Hepatotoxicity
In large clinical trials, the incidence of elevated serum enzymes was not higher in the semaglutide treatment group compared to placebo or control drugs, and no clinically significant cases of liver injury were reported. In fact, semaglutide and other GLP-1 analogues often improve serum transaminase levels (and hepatic steatosis), making it a potential treatment for non-alcoholic fatty liver disease. Since its market launch, no case reports of hepatotoxicity caused by semaglutide have been published, and liver injury is not listed as an adverse event in the product information leaflet. Therefore, if liver injury caused by semaglutide occurs, it must be extremely rare.
Probability score: E (unlikely to cause clinically significant liver injury).
Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
There is currently no information on the clinical use of semaglutide during lactation. Because semaglutide is a peptide molecule with a molecular weight of 4113 Daltons and a protein binding rate of over 99%, its content in breast milk is likely to be very low. The likelihood of infants absorbing this drug is also very low, as it is likely to be destroyed in the infant's gastrointestinal tract. Until more data is available, breastfeeding women should use semaglutide with caution, especially when breastfeeding newborns or premature infants.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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◈ What is semaglutide?
Semaglutide is a medication used to improve glycemic control in adults with type 2 diabetes. It is available in both injectable (administered by injection) and tablet (oral) forms. The injectable form is marketed as Ozempic®, and the tablet form as Rybelsus®. Semaglutide is also available by injection for the treatment of obesity. Semaglutide for weight management is marketed as Wegovy®. Weight loss is not recommended during pregnancy. Please discuss the use of Wegovy® and the best treatment option for you with your healthcare provider. Always consult with your healthcare provider before changing your medication regimen. Your healthcare provider can discuss with you the benefits of treating your condition and the risks of not treating it during pregnancy. Obesity and high/poorly controlled blood sugar can increase the difficulty of conception and the risk of miscarriage, birth defects, or other pregnancy complications. Information sheets about diabetes (https://mothertobaby.org/fact-sheets/type-1-and-type-2-diabetes/) and obesity (https://mothertobaby.org/fact-sheets/obesity-pregnancy/) are available on the MotherToBaby website.
◈ I am currently taking semaglutide, but I want to stop taking it before I get pregnant. How long will this drug stay in my body?
Everyone's drug metabolism rate is different. For healthy adults, it takes an average of about 6 weeks for most semaglutide to be eliminated from the body. The product information leaflets for Ozempic®, Wegovy®, and Rybelsus® recommend that people planning to become pregnant stop taking this medication 2 months before conception.
◈ I am currently taking semaglutide. Will taking semaglutide affect pregnancy?
It is currently unclear whether semaglutide affects pregnancy.
◈ Does taking semaglutide increase the risk of miscarriage?
Miscarriage is common and can occur in any pregnancy for a variety of reasons. There are currently no human studies confirming that semaglutide increases the risk of miscarriage. Animal studies have reported that taking semaglutide increases the risk of miscarriage. It is currently unclear whether this finding is due to the drug itself or weight loss. Because there are many causes of miscarriage, it is difficult to determine whether it is caused by medication, illness, or other factors.
◈ Does taking semagraft increase the risk of birth defects?
There is a 3-5% risk of birth defects in every pregnancy. This is called background risk. Currently, no studies have confirmed whether semagraft increases the risk of birth defects in human fetuses. One case report showed a patient who took semagraft and became pregnant, continuing to take it for the first 3-4 weeks of pregnancy, and ultimately delivered successfully without any birth defects. In animal studies conducted by the manufacturer, an increased risk of certain birth defects has been observed. However, this only occurred when semagraft was administered at maternally toxic doses. Furthermore, it is currently unclear whether the reported birth defects are caused by the drug itself or other factors in the studies (such as weight loss). Because high blood sugar/poor blood sugar control increases the risk of birth defects and other pregnancy complications, it is crucial to weigh the benefits of using semagraft against the risks of not treating high blood sugar. Please discuss the best course of action for treating your condition during pregnancy with your healthcare provider.
◈ Does taking semaglutide during pregnancy increase the risk of other pregnancy-related problems?
Currently, there are no human studies to determine whether semaglutide increases the risk of pregnancy-related problems such as premature birth (delivery before 37 weeks of gestation) or low birth weight (birth weight less than 5 pounds 8 ounces [2500 grams]). Animal studies report that when parent animals received higher doses than humans, their offspring were smaller than normal. It is unclear whether this is due to the drug, weight loss, or because the study animals were healthy enough to remain healthy without taking semaglutide.
◈ Will taking semaglutide during pregnancy affect a child's future behavior or learning abilities?
Currently, there are no studies exploring whether semaglutide causes behavioral or learning problems in children.
◈ Breastfeeding while taking semaglutide:
Currently, there is no information regarding the relationship between semaglutide and breast milk. Based on one animal study, it is expected that a small amount of semaglutide will enter breast milk. Your healthcare provider can discuss the use of semaglutide and the best treatment option for you. Please consult your healthcare professional about all breastfeeding-related questions. The Rybelsus® product label advises that women who are breastfeeding should not use the tablet form of this medication if they are nursing an infant. This is because there is a theoretical concern that using the tablet form of this medication may result in higher drug concentrations in the nursing infant. However, the benefits of using semaglutide likely outweigh the potential risks. Your healthcare provider can discuss with you the use of other dosage forms of semaglutide (tablets or injections) and which treatment option is best for you.
◈ Will men taking semaglutide affect fertility or increase the risk of birth defects?
No human studies have been conducted to determine whether semaglutide affects male fertility (the ability to impregnate a partner) or increases the risk of birth defects (above background risk). One animal study used the same semaglutide dosage as in humans and showed no observed changes in male fertility. Generally, exposure to semaglutide by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, please refer to the “Father Exposure” information sheet on the MotherToBaby website at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein Binding
Semaglutide binds to plasma albumin with high affinity, thus ensuring the high stability of the drug. Its binding rate to albumin exceeds 99%.

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In the SUSTAIN-6 trial, the incidence of gastrointestinal disorders (e.g., nausea, vomiting, diarrhea) in the semaglutide group (50.7%-52.3%) was higher than that in the placebo group (35.2%-35.7%), resulting in a higher proportion of treatment discontinuation due to adverse events. [1]
The incidence of serious adverse events in the semaglutide group (33.6%-35.0%) was lower than that in the placebo group (36.1%-39.9%). [1] The incidence of acute pancreatitis was similar in both groups (9 in the semaglutide group and 12 in the placebo group). The levels of pancreatic enzymes (lipase and amylase) were significantly higher in the semaglutide group than in the placebo group. [1] The overall incidence of malignancies was similar in the semaglutide and placebo groups, but the highest incidence was observed in the 1.0 mg dose group. One case of pancreatic cancer was observed in the semaglutide 1.0 mg group and four cases in the placebo group. No medullary thyroid carcinoma was diagnosed. [1] The incidence of severe or symptomatic hypoglycemia was similar in the semaglutide and placebo groups (approximately 21–23%). [1] Anti-semaglutide antibodies were detected in 30 patients (1.8%), and the antibody titers were generally low and mostly transient. [1]

[1]. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844.

[2]. Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinson's disease mouse model. Neuropeptides. 2018 Oct;71:70-80.

[3]. Semaglutide: First Global Approval. Drugs. 2018 Feb;78(2):275-284.
[4]. In vivo and in vitro characterization of GL0034, a novel long‐acting glucagon‐like peptide‐1 receptor agonist. Diabetes Obes Metab. 2022 Nov; 24(11): 2090–2101.

Novo Nordisk has developed a subcutaneous formulation of semaglutide (Ozempic®), a modified human glucagon-like peptide-1 (GLP-1) analog for the treatment of type 2 diabetes. Developed using Novo Nordisk's proprietary protein acylation technology, the drug is administered via an injection device. Semaglutide lowers blood sugar by stimulating insulin release, while also promoting weight loss. The once-weekly subcutaneous injection of semaglutide was recently approved in the United States, Puerto Rico, and Canada, and has received a positive opinion in the European Union for the treatment of type 2 diabetes. The drug will be marketed as a pre-filled Ozempic® Pen. Semaglutide is also currently under regulatory review in Japan and Switzerland for the treatment of type 2 diabetes. Clinical development for obesity, non-alcoholic steatohepatitis (NAHH), and non-alcoholic fatty liver disease (NAFLD) is underway globally. This article summarizes the key milestones in the development of semaglutide, culminating in its first approval for the treatment of type 2 diabetes. [3]

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In patients with type 2 diabetes at high cardiovascular risk, the incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower in patients treated with semaglutide than in patients treated with placebo, confirming the non-inferiority of semaglutide. [2]

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Semaglutide is a polypeptide composed of 31 amino acids linked by peptide bonds. It is an agonist of glucagon-like peptide-1 receptor (GLP-1 AR) and is used to treat type 2 diabetes. It has multiple effects, including hypoglycemic, glucagon-like peptide-1 receptor agonist, anti-obesity, neuroprotective, and appetite-suppressing effects. It is a polypeptide and lipopeptide.
Semaglutide is a glucagon-like peptide-1 (GLP-1) analog used to treat type 2 diabetes and requires lifestyle modifications, such as dietary restrictions and increased physical activity. Other members of this class of drugs include exenatide and liraglutide. Semaglutide, developed by Novo Nordisk, was approved by the U.S. Food and Drug Administration (FDA) for subcutaneous injection in December 2017. Tablets were approved for oral administration in September 2019. Semaglutide works by binding to and activating the GLP-1 receptor, thereby stimulating insulin secretion and lowering blood sugar. Subcutaneous injection is administered once weekly, and tablets once daily. Semaglutide has a competitive advantage compared to other diabetes treatments that may require multiple daily doses. Clinical trials have shown that the drug reduces glycated hemoglobin (HbA1c) levels and promotes weight loss in patients with type 2 diabetes. In June 2021, the FDA approved semaglutide for the treatment of chronic weight management in obese or overweight adults with at least one weight-related disease, the first drug approved for this purpose since 2014. Health Canada and the European Medicines Agency (EMA) have also approved semaglutide for weight management. On May 31, 2023, the FDA issued a warning regarding the use of semaglutide after receiving an adverse event report. The safety and efficacy of salt forms of semaglutide, including semaglutide sodium and semaglutide acetate, have not been established.

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Semaglutide is a GLP-1 receptor agonist. The mechanism of action of semaglutide is as a glucagon-like peptide-1 (GLP-1) receptor agonist.
Smegglutide is a recombinant DNA-produced polypeptide, an analogue of human glucagon-like peptide-1 (GLP-1), used in combination with diet and exercise to treat type 2 diabetes, either alone or in combination with other antidiabetic drugs. There are currently no reports of hepatotoxicity associated with smegglutide treatment. Smegglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist with 94% homology to human GLP-1 (7-37), and has hypoglycemic and appetite-regulating effects. After administration, smegglutide binds to and activates the GLP-1 receptor. In pancreatic β-cells, this increases glucose-dependent insulin release. Smegglutide reduces elevated glucagon secretion by inhibiting pancreatic α-cells and delays gastric emptying. These effects collectively lower postprandial blood glucose levels. In the brain, smegglutide binds to and activates the GLP-1 receptor, thereby suppressing appetite, reducing calorie intake, and decreasing weight. GLP-1 is normally secreted by L cells in the gastrointestinal mucosa after meals to normalize blood glucose levels. It also plays an important role in regulating appetite and calorie intake. Smegglutide is indicated for improving glycemic control in adults with type 2 diabetes and as an adjunct to diet and exercise. However, smegglutide is not a first-line treatment for diabetic patients whose blood glucose cannot be controlled by diet and exercise. Furthermore, it has not been studied in patients with pancreatitis. Smegglutide is not indicated for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Smegglutide is indicated for long-term weight management in obese or overweight adults with at least one weight-related condition (e.g., hypertension, type 2 diabetes, or high cholesterol), requiring a low-calorie diet and increased physical activity. Smegglutide is also indicated for long-term weight management in children aged 12 years and older with an initial BMI at or above the 95th percentile for their age and sex. Smegglutide can reduce glycated hemoglobin (HbA1c), systolic blood pressure, and body weight. After 12 weeks of treatment, semaglutide lowers fasting and postprandial blood glucose by increasing insulin secretion and decreasing glucagon secretion (glucagon secretion is typically associated with elevated blood glucose). Semaglutide also lowers fasting triglycerides and very low-density lipoprotein cholesterol (VLDL-C), thus having a beneficial effect on cardiovascular health. Studies have shown that semaglutide can induce medullary thyroid carcinoma in rodents. Although its clinical significance in humans is unclear, the FDA recommends that patients with a personal or family history of medullary thyroid carcinoma should not use this drug. Semaglutide also carries the risk of pancreatitis and dehydration. Patients must maintain adequate hydration while taking semaglutide, and if abdominal pain radiating to the back occurs, immediate medical attention is recommended. Because this drug delays gastric emptying, the efficacy or adverse reactions of other oral medications must be monitored.

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Mechanism of Action:
Glucose Control Mechanism GLP-1 is a physiological hormone that promotes glycemic control through multiple mechanisms, including promoting insulin secretion, delaying gastric emptying, and reducing postprandial glucagon secretion. Glucose homeostasis depends on hormones such as insulin and amylin, which are secreted by pancreatic β-cells. Semaglutide has 94% similarity to human GLP-1. Analogs of this hormone, such as semaglutide, stimulate insulin synthesis by stimulating pancreatic islet cells and reducing glucagon secretion. They selectively bind directly to GLP-1 receptors, producing a variety of beneficial downstream effects, lowering blood glucose in a glucose-dependent manner. Mechanisms of Cardiovascular Benefits and Weight Loss In hypercholesterolemia, semaglutide is thought to slow the progression of atherosclerosis by reducing intestinal permeability and inflammation. Weight loss is thought to be due to decreased appetite and food cravings after semaglutide administration. Hepatotoxicity: In large clinical trials, the incidence of elevated serum enzymes was not higher in the semaglutide treatment group than in the placebo or control groups, and no clinically manifested cases of liver injury were reported. In fact, treatment with semaglutide and other GLP-1 analogs often improves serum transaminase levels (and hepatic steatosis), making it a potential treatment for non-alcoholic fatty liver disease. Since its approval, no case reports of hepatotoxicity caused by semaglutide have been published, and liver injury is not listed as an adverse event on the product label. Therefore, liver injury caused by semaglutide, even if it occurs, must be extremely rare.

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Semaglutide is a glucagon-like peptide-1 (GLP-1) analog used to treat type 2 diabetes. This report comes from the SUSTAIN-6 trial, a premarket cardiovascular outcome trial designed to assess cardiovascular safety.
[1]
The trial demonstrated that semaglutide was non-inferior to placebo in terms of cardiovascular risk and showed a significant advantage in reducing major composite cardiovascular endpoint events in high-risk patients with type 2 diabetes. [1]
Increased risk of retinopathy complications is considered a safety signal, which may be related to rapid reduction in blood glucose, but the direct effect of the drug cannot be ruled out. [1]
Beneficial cardiovascular effects may be related to improvements in blood glucose control, weight, systolic blood pressure, and potential changes in the progression of atherosclerosis. [1]

C189H292F3N45O61

4227.66

910463-68-2 (Semaglutide free base); 1997361-85-9 (Semaglutide acetate); 2924330-56-1 (sodium)

H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH

HXEGTFTSDV SSYLEGQAAK EFIAWLVRGR G

White to off-white solid powder

NNC 0113-0217 TFA; NNC 0113-0217; NNC-0113-0217; NNC-0113 0217

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Please refer to the "Guidelines for Dissolving Peptides" section in the 4th page of the "Instructions for use" file (upper-right section of this webpage) for how to dissolve peptides.

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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.

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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 : 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).

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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 : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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

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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.

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