VEGFR2 (IC50 = 40 nM); VEGFR3 (IC50 = 110 nM); EGFR/HER1 (IC50 = 500 nM)

Vandetanib suppresses EGFR and VEGFR3 with IC50 values of 500 nM and 110 nM, respectively. Vandetanib almost completely lacks activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt, and IGF-1R, with an IC50 above 10 μM. It is insensitive to PDGFRβ, Flt1, Tie-2, and FGFR1. Vandetanib has no effect on basal endothelial cell growth but inhibits the proliferation of HUVECs stimulated by VEGF, EGF, and bFGF at IC50 values of 60 nM, 170 nM, and 800 nM. With an IC50 range of 2.7 μM (A549) to 13.5 μM (Calu-6)[1], vandetanib inhibits the growth of tumor cells. In a mouse B cell line, odanacatib's antigen presentation inhibitory activity was found to be weak (IC50=1.5±0.4 μM) in contrast to the Cat S inhibitor LHVS (IC50=0.001 μM) in the same assay. Additionally, odanacatib exhibits a weaker inhibitory effect on the MHC II invariant chain protein Iip10 processing in mouse splenocytes when compared to LHVS (minimum inhibitory concentrations of 1–10 μM versus 0.01 μM, respectively)[2]. Vandetanib prevents cell growth by suppressing the phosphorylation of EGFR in hepatoma cells and VEGFR-2 in HUVECs[4].

Vandetanib (15 mg/kg, p.o.) inhibits tumor growth with an IC50 of 3.5±1.2 μM, showing a superior anti-tumor effect over gefitinib in the H1650 xenograft model[3]. Vandetanib (50 or 75 mg/kg) significantly lowers tumor vessel density, increases tumor cell apoptosis, suppresses tumor growth, increases survival, decreases the number of intrahepatic metastases, and upregulates VEGF, TGF-α, and EGF in tumor tissues in tumor-bearing mice[4]. It also suppresses the phosphorylation of VEGFR-2 and EGFR in tumor tissues.

In 96-well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate, vandetanib is incubated with the enzyme, 10 mM MnCl₂, and 2 μM ATP. The next step is to identify phosphorylated tyrosine by sequentially incubating 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), a horseradish peroxidase-linked sheep antimouse immunoglobulin antibody, and a mouse IgG anti-phosphotyrosine 4G10 antibody. To investigate selectivity against tyrosine kinases linked to FGFR1, c-kit, erbB2, IGF-1R, FAK, PDGFRβ, Tie-2, and FGFR1, this methodology is modified. Appropriate ATP concentrations at or slightly below the corresponding Km (0.2–14 μM) were used in all enzyme assays (tyrosine or serine–threonine). Selectivity against serine-threonine kinases (CDK2, AKT, and PDK1) is investigated in 96-well plates using a pertinent scintillation proximity-assay (SPA). The conditions for the CDK2 assays were as follows: 10 mM MnCl₂, 4.5 μM ATP, 0.15 μCi of [γ-³³ P]ATP/reaction, 50 mM HEPES (pH 7.5), 1 mM DTT, 0.1 mM sodium orthovanadate, 0.1 mM sodium fluoride, 10 mM sodium glycerophosphate, 1 mg/mL BSA fraction V, and a retinoblastoma substrate (a portion of the retinoblastoma gene, 792–928, expressed in a glutathione S-transferase expression system; 0.22 μM initial concentration). The reactions are conducted at room temperature for 60 minutes and then quenched for two hours using 150 μL of a solution that contains 0.8 mg/reaction of protein A SPA-polyvinyltoluene beads, 3 μg of rabbit immunoglobulin anti-glutathione S-transferase antibody, and EDTA (62 mM final concentration). After that, the plates are sealed, centrifuged for five minutes at 1200 x g, and counted for thirty seconds using a Microplate scintillation counter.

The MTT assay is modified to measure growth inhibition. In a nutshell, the cells are exposed to either vandetanib or gefitinib for 72 hours after being plated at a density of 2000 cells per well in 96-well plates. Triples of each assay are run. For every medication, the 50% inhibitory concentration (IC50) is calculated using the mean±standard deviation (SD).

Absorption, Distribution and Excretion
Slow absorption—median peak plasma concentration is reached in 6 hours. After multiple doses, vandetanib plasma concentrations can accumulate to approximately 8-fold, reaching steady state after about 3 months. Approximately 69% of the drug is recovered 21 days after a single dose of vandetanib. Of this, 44% is found in feces and 25% in urine. Volume of distribution (Vd) is approximately 7450 liters. Vandetanib binds to human serum albumin and α1-acid glycoprotein, with an in vitro protein binding rate of approximately 90%. After reaching steady state with a once-daily dose of 300 mg vandetanib in colorectal cancer patients, the average protein binding rate in ex vivo plasma samples was 94%. Approximately 69% of the drug is recovered during the 21-day collection period after a single dose of ¹⁴C-vandetanib, with 44% found in feces and 25% in urine. Excretion of this dose is slow, and based on the plasma half-life, it is expected to continue to be excreted after 21 days. Vandetanib is not a substrate of hOCT2 expressed in HEK293 cells. Vandetanib inhibits the uptake of the selective OCT2-labeled substrate 14C-creatinine by HEK-OCT2 cells, with a mean IC50 of 2.1 μg/mL. This value is higher than the vandetanib plasma concentration (0.81 μg/mL) observed after multiple 300 mg doses. Vandetanib inhibits renal excretion of creatinine, which may explain the elevated plasma creatinine levels in subjects treated with vandetanib.
After oral administration of capreressa, absorption is slow, and peak plasma concentrations are typically reached 6 hours (median, range 4–10 hours) after administration. After multiple doses, vandetanib plasma concentrations can accumulate to approximately 8-fold, reaching steady state after approximately 3 months. Food does not affect vandetanib exposure.
The protein binding rate of ¹⁴C-vandetanib in the plasma of mice, rats, rabbits, dogs, and humans is moderate, ranging from 83% to 90%. Following a single oral administration, vandetanib and/or its metabolites exhibit slow but widespread tissue distribution in colored and colorless male rats, consistent with the distribution pattern of lipophilic compounds. Peak concentrations of vandetanib and/or its metabolites are reached in most tissues 6–8 hours post-administration. The radioactive material is prominently distributed in brain tissue. Retention of the radioactive material was observed in colored tissues, indicating its affinity for melanin. Significant radioactive distribution was observed in the milk of lactating rats and in the plasma of lactating pups.
For more complete data on the absorption, distribution, and excretion of vandetanib (8 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Unmetabolized vandetanib and its metabolites vandetanib N-oxide and N-desmethylvandetanib were detected in plasma, urine, and feces. N-desmethylvandetanib was primarily produced by CYP3A4, while vandetanib N-oxide was primarily produced by the flavin-containing monooxygenases FMO1 and FMO3.
The metabolism of vandetanib appeared similar in the toxicological study species (rats and dogs) as well as in mice and humans. The two major metabolites identified in excrement were N-desmethylvandetanib and vandetanib N-oxide. In mice, a minor metabolite, O-desalkylvandetanib glucuronide, was also identified. Glucuronide conjugates were also detected in human urine. Metabolism and bile excretion appear to be the main pathways of vandetanib clearance in preclinical animal models. In vitro CYP identification studies indicated that CYP3A4 is involved in the formation of N-desmethylvandetanib. Vandetanib-N-oxide is generated by FMO1 and FMO3 (FMO = flavin monooxygenase). These two enzymes are also present in the kidneys, suggesting that renal excretion may contribute to vandetanib clearance. Following oral administration of (14)C-vandetanib, unchanged vandetanib and its metabolites vandetanib-N-oxide and N-demethylvandetanib were detected in plasma, urine, and feces. Glucuronide conjugates were only found as minor metabolites in excretions. N-demethylvandetanib was primarily generated by CYP3A4, while vandetanib-N-oxide was generated by the flavin monooxygenases FMO1 and FMO3. The circulating concentrations of N-demethylvandetanib and vandetanib-N-oxide were approximately 7-17% and 1.4-2.2% of vandetanib, respectively. ...At all time points, the total radioactivity concentration in plasma was higher than that of vandetanib, indicating the presence of circulating metabolites. Unmetabolized vandetanib and two expected metabolites (N-demethylvandetanib and vandetanib-N-oxide) were detected in plasma, urine, and feces. Additionally, a trace metabolite (glucuronide conjugate) was found in urine and feces. Unmodified vandetanib and its N-demethyl and N-oxide metabolites were detected in plasma, urine, and feces.

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Biological half-life
The median half-life is 19 days.
...In patients with medullary thyroid carcinoma (MTC), a 300 mg dose of capreressa is characterized by...a median plasma half-life of 19 days.
...Vandertanib is slowly absorbed and eliminated, with a half-life of approximately 10 days after a single oral dose.

Toxicity Summary
Identification and Use: Vandetanib is a white to off-white powder, formulated as film-coated tablets. Vandetanib is a multi-target tyrosine kinase inhibitor used to treat patients with locally advanced or metastatic, unresectable symptomatic or progressive medullary thyroid carcinoma. Due to the risks of QT interval prolongation, torsades de pointes, and sudden death, the U.S. Food and Drug Administration (FDA) requires a Risk Assessment and Mitigation Strategy (REMS) for vandetanib. Under the terms of the REMS program, vandetanib is only available through a restricted distribution program. The FDA has granted it orphan drug designation. Human Exposure and Toxicity: Vandetanib prolongs the QT interval in a concentration-dependent manner. Patients treated with vandetanib have reported torsades de pointes (a distinctive polymorphic ventricular tachycardia characterized by QRS amplitude variations and torsional QRS complexes), ventricular tachycardia, and sudden death. Vandetanib should not be used in patients with a history of torsades de pointes, congenital long QT syndrome, bradycardia, or decompensated heart failure, nor in patients with electrolyte disturbances. Hypocalcemia, hypokalemia, and/or hypomagnesemia must be corrected before using vandetanib. Other toxicities associated with vandetanib use include severe skin reactions (including Stevens-Johnson syndrome), interstitial lung disease or pneumonia, ischemic cerebrovascular events, severe bleeding events, and heart failure, which may also lead to death. Vandetanib may also harm the fetus if used in pregnant women. Therefore, pregnancy should be avoided during vandetanib treatment. Vandetanib has no chromosome-breaking effect on cultured human lymphocytes. Animal studies: In rats, a single oral dose of 2000 mg/kg was intolerable, and all animals died on day 4 or were euthanized for humane reasons. Histopathological findings in these rats included hepatocyte vacuolation, fat deposition and liver necrosis, gastric ulcers, duodenal mucosal monocellular necrosis and erosion, and splenic macrophage vacuolation. No adverse reactions were observed in the 1000 mg/kg dose group. Mice could not tolerate a single oral dose of 2000 mg/kg, and all animals died on day 1 or were euthanized for humane reasons. A single oral dose of 1000 mg/kg resulted in the death of 1 in 10 mice. No other significant histopathological changes were observed except for gastric ulceration in one animal receiving the 2000 mg/kg dose. Dose-limiting toxicities in the 1-month, 6-month, and 9-month studies included gastrointestinal reactions in dogs (including loose/abnormal stools, vomiting, and weight loss) and skin and hepatotoxicity in rats. Vandetanib had no effect on mating or fertility in male rats, while female rats showed a trend toward increased estrous cycle disturbances, a slightly decreased pregnancy rate, and an increased risk of post-implantation embryo loss. In rats, vandetanib showed a potential risk of embryo-fetal loss, fetal growth retardation, cardiovascular abnormalities, and premature ossification of parts of the skull. In a rat prenatal and postnatal development study, at doses that produced maternal toxicity during pregnancy and/or lactation, vandetanib increased prenatal loss and reduced postnatal growth in pups. Vandetanib did not show mutagenicity in four Salmonella Typhimurium strains (TA1535, TA1537, TA98, and TA100) and two Escherichia coli strains (WP2P and WP2 uvrA), regardless of metabolic activation.
Hepatotoxicity
In large clinical trials of vandetanib, abnormalities in routine liver function tests were common, with elevated serum transaminases occurring in up to half of patients, and 2% to 5% of patients having transaminase levels exceeding five times the upper limit of normal (ULN). In premarketing trials of vandetanib for the treatment of thyroid cancer, no clinically significant liver injury (such as jaundice or liver failure) was reported. Since its approval and widespread use, no published reports of vandetanib causing hepatotoxicity have been found, and the product information does not mention hepatotoxicity. However, many kinase inhibitors used in cancer chemotherapy have been associated with clinically significant liver injury cases, which typically occur within the first 2 to 12 weeks of treatment, manifesting as symptoms such as fatigue, nausea, and jaundice, as well as elevated serum enzymes in a hepatocellular pattern, but without immune hypersensitivity or autoimmune features. Some tyrosine kinase inhibitors (imatinib, nilotinib) have also been associated with hepatitis B virus reactivation.
Probability Score: E (Unconfirmed, but suspected as a rare cause of clinically significant liver injury).
Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
There is currently no information regarding the clinical use of vandetanib during lactation. Because vandetanib binds to plasma proteins at a rate of up to 90%, its concentration in breast milk is likely to be low. However, its half-life of 19 days may allow it to accumulate in the infant. The manufacturer recommends discontinuing breastfeeding during vandetanib treatment and for 4 months after the last dose.
◉ 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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Protein binding
Protein binding is approximately 90%.

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Drug interactions
Vandertanib is concomitant with drugs known to prolong the QT interval, including class Ia drugs (e.g., disopyramide, procainamide, quinidine) and class III drugs. Antiarrhythmic drugs (e.g., amiodarone, sotalol, dofetilide), certain anti-infective drugs (e.g., clarithromycin, gatifloxacin, moxifloxacin), certain antipsychotic drugs (e.g., chlorpromazine, thioridazine, haloperidol, asenapine, olanzapine, paliperidone, pimozide, quetiapine, ziprasidone, etc.), and some type 3 serotonin (5-HT3) receptor antagonists used as antiemetics (e.g., dolasetron, granisetron, ondansetron), chloroquine, methadone, and buphenazine. If it is necessary to use known... For medications that prolong the QT interval, it is recommended to increase the frequency of ECG monitoring. If a 5-HT3 receptor antagonist is clinically necessary, some clinicians prefer granisetron because its effect on the ECG interval is less than that of dolasetron or ondansetron. CYP3A4 inducers can alter the plasma concentration of vandetanib. Vandetanib should be avoided in combination with potent CYP3A4 inducers (such as carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine). Hypericum (St. John's wort) Perforatum may unpredictably reduce vandetanib exposure; therefore, concomitant use of vandetanib with this drug should also be avoided. Capresexa increases digoxin plasma concentrations. Caution should be exercised when using capresexa with digoxin, and close monitoring for toxic reactions is necessary. Capresexa increases metformin plasma concentrations transported by organic cation transporter 2 (OCT2). Caution should be exercised when using capresexa with drugs transported by OCT2, and close monitoring for toxic reactions is necessary.

[1]. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 2002 Aug 15;62(16):4645-55.

[2]. Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance. Biochem Pharmacol. 2012 Aug 1;84(3):260-7.

[3]. Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency. Exp Cell Res. 2013 Feb 15;319(4):417-23.

[4]. Vandetanib, an inhibitor of VEGF receptor-2 and EGF receptor, suppresses tumor development and improves prognosis of liver cancer in mice. Clin Cancer Res. 2012 Jul 15;18(14):3924-33.

Therapeutic Uses
Anti-tumor Drug Caprelsa is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid carcinoma in patients with unresectable locally advanced or metastatic medullary thyroid carcinoma. /US Product Label Includes/ Due to the risks of QT interval prolongation, torsades de pointes, and sudden cardiac death, the US Food and Drug Administration (FDA) requires and has approved a Risk Assessment and Mitigation Strategy (REMS) for vandetanib. Under the terms of the REMS program, vandetanib is only available through a restricted distribution program (Caprelsa REMS program). Prescribing physicians and pharmacies must be certified under the Caprelsa REMS program to prescribe or dispense vandetanib. To be certified, prescribing physicians must read the educational materials, agree to comply with REMS requirements, and register for the program. Pharmacies distributing vandetanib must join the program, train their pharmacy staff to verify that each prescription is written by a qualified prescribing physician before dispensing the medication to patients, and agree to comply with the Risk Assessment and Mitigation Strategy (REMS) requirements. Vandetanib is used to treat patients with locally advanced or metastatic, unresectable symptomatic or progressive medullary thyroid carcinoma; vandetanib has been designated an orphan drug by the U.S. Food and Drug Administration (FDA) for the treatment of this cancer.

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Drug Warnings
/Black Box Warning/ Warning: QT interval prolongation, torsades de pointes, and sudden death. Caprelsa can prolong the QT interval. Torsades de pointes and sudden death have occurred in patients treated with caprelsa. Caprelsa is contraindicated in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Hypocalcemia, hypokalemia, and/or hypomagnesemia should be corrected before taking caprelsa. Monitor electrolyte levels regularly. Avoid use of drugs known to prolong the QT interval. Caprelsa can only be prescribed and dispensed by physicians and pharmacies with restricted distribution program certification. Vandetanib prolongs the QT interval in a concentration-dependent manner. Patients treated with vandetanib have reported experiencing torsades de pointes, ventricular tachycardia, and sudden cardiac death. In a phase 3 clinical trial, patients randomized to receive vandetanib (300 mg once daily) had a mean QT interval (QTcF, adjusted for heart rate using the Fridericia formula) prolongation of 35 ms from baseline (range: 33–36 ms); throughout the study period (up to 2 years), the QTcF prolongation consistently exceeded 30 ms. Furthermore, 36% of patients treated with vandetanib experienced a QTcF increase of more than 60 ms from baseline, and 69% and 7% of patients, respectively, had QTcF increases exceeding 450 ms and 500 ms. Patients treated with caprexa have experienced interstitial lung disease (ILD) or pneumonia, including cases of death. For patients presenting with nonspecific respiratory signs and symptoms, a diagnosis of ILD should be considered. Capresexa should be discontinued if acute or worsening pulmonary symptoms occur. If ILD is diagnosed, capresexa should be discontinued.
There have been reports of ischemic cerebrovascular events (sometimes fatal) associated with vandetanib treatment. In a phase 3 clinical trial, the incidence of ischemic cerebrovascular events was higher in the vandetanib group compared to the placebo group (1.3% vs. 0%); all ischemic cerebrovascular events reported in this study were grade 3. Vandetanib should be discontinued in patients experiencing a serious ischemic cerebrovascular event. The safety of restarting vandetanib treatment after resolution of an ischemic cerebrovascular event has not been investigated.
For more complete data on vandetanib warnings (out of 20), please visit the HSDB record page.

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Pharmacodynamics
Mean IC50 is approximately 2.1 μg/mL.

C26H28BRFN4O6

475.35396

474.106

C, 52.80; H, 4.77; Br, 13.51; F, 3.21; N, 9.47; O, 16.23

338992-00-0

443913-73-3;338992-00-0 (fumarate); 338992-00-0; 338992-53-3; 524722-52-9

3081361

Typically exists as solid at room temperature

1.4±0.1 g/cm3

538.2±50.0 °C at 760 mmHg

279.3±30.1 °C

0.0±1.4 mmHg at 25°C

1.629

5.51

1

7

6

30

539

0

NEJYMTWEAISFSJ-WLHGVMLRSA-N

InChI=1S/C22H24BrFN4O2.C4H4O4/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)245-3(6)1-2-4(7)8/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)1-2H,(H,5,6)(H,7,8)/b2-1+

N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Fumarate

Caprelsa; HSDB 8198; Zactima; ZD-6474; Vandetanib; 443913-73-3; Zactima; ZD6474; Caprelsa; N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine; ZD-6474; N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine; ZD 6474; ZD6474

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)

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

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.)