sst1 ( pKi = 8.2 ); sst2 ( pKi = 9.0 ); sst3 ( pKi = 9.1 ); sst4 ( pKi < 7.0 ); sst5 ( pKi = 9.9 )

Pasireotide binds to human somatostatin receptors with a unique high affinity (subtypes sst1/2/3/4/5, pKi=8.2/9.0/9.1/<7.0/9.9, respectively)[1].
Pasireotide suppresses the growth hormone releasing hormone (GHRH)-induced release of growth hormone (GH) in primary cultures of rat pituitary cells, with an IC50 of 0.4 nM[1].

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The strategy pursued in this research has been rewarded with the demonstrated superiority of Pasireotide/25 compared to 2. Pharmacological studies in vitro have clearly shown that Pasireotide/25 effectively inhibited the growth hormone releasing hormone (GHRH) induced growth hormone (GH) release in primary cultures of rat pituitary cells with an IC50 of 0.4 ± 0.1 nmol/L (n = 5) [1].

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Pasireotide is a somatostatin analogue with high binding affinity to somatostatin receptor subtypes sst1,2,3 and sst5, as shown in competitive binding studies using CHO-K1 cells expressing human recombinant somatostatin receptors (Table 2) (Bruns et al., 2002, Schmid and Schoeffter, 2004). In CCL39 cells expressing human recombinant sst receptors, pasireotide and somatostatin (SRIF-14) inhibited forskolin-stimulated cAMP accumulation with approximately the same efficacy and potency. Compared with octreotide, the functional activity (based on EC50 values) of pasireotide on sst1, sst3 and sst5 was >30-, 11- and 158-fold higher, respectively, but 7-fold lower on sst2 (Schmid and Schoeffter, 2004).
Based on the differences in binding affinity and functional activity of Pasireotide and octreotide, it can be speculated that in cells and tissues that express sst receptors other than the sst2 receptor subtype, pasireotide will have a stronger inhibitory effect on hormone secretion than octreotide [3].

Pasireotide (160 mg/kg/mouth; s.c. for 4 months) dramatically lowers serum insulin, raises serum glucose, shrinks tumor size, and accelerates apoptosis in Pdx1-Cre[2].
Pasireotide (2-50 μg/kg; s.c. twice daily for 42 days) acts through the SSTR2 receptor to produce antinociceptive and anti-inflammatory effects in a mouse model of immune-mediated arthritis[4].

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In vivo, Pasireotide/25 also potently suppressed GH secretion in rats. The ED50 values determined at 1 and 6 h after injection of 25 indicated its very long duration of action in vivo. In the rat, 25 strongly decreases IGF-1 plasma levels, with the efficacy being markedly enhanced compared with the effects elicited by 2 after 7 days of treatment. Furthermore, in rats, dogs, and rhesus monkeys, 25 potently and dose-dependently decreased IGF-1 levels for prolonged periods of time without desensitization as observed with SMS 201-995 (2).[1]

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Background: Pasireotide (SOM230), a long-acting somatostatin analogue (LAR), has improved agonist activity at somatostatin receptors. We tested the effect of SOM230 on insulin secretion, serum glucose concentrations, tumor growth, and survival using an MEN1 transgenic mouse model.
Methods: Eight 12-month-old conditional Men1 knockout mice with insulinoma were assessed. The treatment (n = 4) and control groups (n = 4) received monthly subcutaneous injections of SOM230 or PBS. Serum insulin and glucose levels were determined by enzyme-linked immunosorbent assay and enzymatic colorimetric assay, respectively. Tumor activity, growth, and apoptosis were determined by microPET/CT scan and histologic analysis.
Results: On day 7, there was a decrease in serum insulin levels from 1.06 ± 0.28 μg/L to 0.37 ± 0.17 μg/L (P = .0128) and a significant increase in serum glucose from 4.2 ± 0.45 mmol/L to 7.12 ± 1.06 mmol/L (P = .0075) in the treatment group but no change in the control group. Tumor size was less in the treatment group (2,098 ± 388 μm(2)) compared with the control group (7,067 ± 955 μm(2); P = .0024). Furthermore, apoptosis was increased in the treatment group (6.9 ± 1.23%) compared with the control group (0.29 ± 0.103%; P = .002).
Conclusion: SOM230 demonstrates antisecretory, antiproliferative, and proapoptotic activity in our MEN1 model of insulinoma. Further studies of the effects of SOM230 in PNET patients with MEN1 mutations are warranted.[2]

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Objective: Clinical and preclinical evidence suggests that somatostatin exhibits potent antiinflammatory and antinociceptive properties. However, it is not known which of the 5 somatostatin receptor subtypes (SSTRs 1-5) is involved in these actions. The purpose of this study was to assess the effects of the stable somatostatin analogs octreotide and Pasireotide (SOM230) in a mouse model of antigen-induced arthritis (AIA).
Methods: Studies were performed in SSTR2-deficient mice (SSTR2(-/-)) and their wild-type littermates (SSTR2(+/+)). The expression of SSTR1, SSTR2A, SSTR3, and SSTR5 in dorsal root ganglia was examined by immunohistochemistry.
Results: Untreated SSTR2(-/-) mice with AIA displayed joint swelling and mechanical hyperalgesia similar to that seen in SSTR2(+/+) mice. In wild-type mice, both octreotide and Pasireotide significantly attenuated knee joint swelling and histopathologic manifestations of arthritis to an extent comparable to that of dexamethasone. In SSTR2(-/-) mice, the antiinflammatory effects of both octreotide and pasireotide were completely abrogated. Prolonged administration of Pasireotide also inhibited joint swelling and protected against joint destruction during AIA flare reactions. In addition, both octreotide and pasireotide reduced inflammatory hyperalgesia. The antinociceptive actions of octreotide were abolished in SSTR2(-/-) mice, but those of pasireotide were retained. In dorsal root ganglia of naive wild-type mice, only SSTR1 and SSTR2A, but not SSTR3 or SSTR5, were detected in a subset of small- and medium-diameter neurons.
Conclusion: Our findings indicate that the antinociceptive and antiinflammatory actions of octreotide and Pasireotide are largely mediated via the SSTR2 receptor. In addition, we identified the SSTR1 receptor as a novel pharmacologic target for somatostatin-mediated peripheral analgesia in inflammatory pain [4].

Pharmacological Characterization. Radioligand Binding Assays. [1]
Radioligand binding assays were performed as described previously. Briefly, membranes from CHO and COS cells expressing the respective human SRIF receptor subtype were incubated with the SRIF receptor ligand Tyr11[125I]-SRIF in the presence or absence of various concentrations of SRIF receptor ligands. The incubation was stopped after 1 h by rapid filtration through Whatman GF/C filters. Inhibition curves were analyzed, and IC50 values were calculated.

Apoptosis analysis [2]
Apoptotic status in endocrine tumor tissues was measured in control and treated mice by Terminal deoxynucleotidyl transferase dUTP Nick End-Labeling (TUNEL) assay. For quantification of apoptosis, the TUNEL assay was performed according to the manufacturer on paraffin-embedded sections with an In Situ Cell Death Detection Kit. The tissue sections were deparaffinized and treated with proteinase K (10 μg/ml) for 20 min. The sections were then washed twice with PBS, labeled and stained with the TUNEL reaction mixture (label plus enzyme solutions) for 60 min at 37°C, and washed twice with PBS in the dark. The slides were mounted in Vectashield mounting medium with DAPI. The apoptotic fluorescent cells were counted under a fluorescent microscope and the numbers were expressed as the percentage of total cells ± standard deviation (SD). A negative control without enzyme treatment and a positive control with DNase I treatment were also performed.

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SSTR detection [2]
The detection of sstr1-5 in pancreatic endocrine tumor tissue was measured in our mouse model. Immunofluorescent (IF) staining for sstr1-5 on sections was performed using rabbit or goat anti-sstr1, sstr2, sstr3, sstr4, and sstr5 antibodies (Abs) and were incubated at a 1:50 dilution overnight at 4° C, respectively. Pig anti-insulin Ab was also used for identification of β-cells. Sections were then washed with PBS and were incubated with a 1:200 dilution of anti-rabbit or anti-goat Alexa Fluor 488 and anti-pig Alexa Fluor 647 secondary antibodies for 45 min in the dark, respectively. A negative control without primary antibody was also performed.

12 month-old conditional Men1 knockout mice with insulinoma
160 mg/kg/mouth
S.c. every month for 4 months

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SOM230/Pasireotide and PBS Administration [2]
Mice were anesthetized using halothane and then shaved on their flank for subcutaneous injection of either phosphate buffered saline (PBS) buffer or Pasireotide/SOM230 at a concentration of 160mg/Kg/month (64mg/ml) every month for 4 months.

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Treatment protocol and drugs. [4]
Mice were randomly allocated to the following groups (8–10 animals per experimental condition): 0.9% saline; 2, 20, or 50 μg/kg of octreotide; or 2, 20, or 50 μg/kg of Pasireotide. These doses have been shown to elicit long-lasting therapeutic effects on pituitary hormone secretion in rodents and humans. Octreotide and Pasireotide were a kind gift from Novartis and were administered subcutaneously in a volume of 0.1 ml/kg of body weight. Treatment was started 12 hours before the induction of AIA and was continued for 3, 21, or 42 days, with administration every 12 hours for the indicated time periods. Flare reactions were provoked by injecting the right knee joint cavity with 100 μg of mBSA dissolved in 20 μl of PBS on days 21 and 35 of AIA. An additional group received 0.6 mg/kg of dexamethasone palmitate by intraperitoneal injection. Dexamethasone treatment was carried out for 5 days, followed by a 2-day pause starting 12 hours before AIA induction.

Absorption, Distribution and Excretion
Peak plasma concentrations of parecide are reached within 0.25–0.5 hours. Cmax and AUC increase proportionally to the dose after single and multiple administrations. Parecide is primarily cleared by the liver (biliary excretion) (approximately 48%), with a small amount cleared by the kidneys (approximately 7.63%). Parecide has a wide distribution, with a volume of distribution >100 L. The clearance rate in healthy subjects is approximately 7.6 L/h, and in patients with Cushing's disease, it is approximately 3.8 L/h. Metabolisms/Metabolites Metabolism is minimal. Biological Half-Life The half-life is 12 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
The secretion of paretin into breast milk has not been studied. However, due to its high molecular weight of 1047 Daltons, very little is likely secreted into breast milk, and as a peptide drug, it is likely to be digested in the infant's gastrointestinal tract. It is unlikely to reach clinically significant concentrations in infant serum. However, the manufacturer states that paretin should not be used by breastfeeding women. Alternative medications are recommended.
◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.

[1]. A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential. J Med Chem. 2003 Jun 5;46(12):2334-44.

[2]. Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model. Surgery. 2012 Dec;152(6):1068-77.

[3]. Pasireotide (SOM230): development, mechanism of action and potential applications. Mol Cell Endocrinol. 2008 May 14;286(1-2):69-74.

[4]. Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune-mediated arthritis. Arthritis Rheum. 2011 Aug;63(8):2352-62.

Pasireotide aspartate is the diaspartate salt of Pasireotide, belonging to the aspartate class. It is a somatostatin analog with pharmacological properties similar to the natural hormone somatostatin, used to treat Cushing's disease. It can be used as an antitumor drug and prodrug. It contains Pasireotide (2+).
See also: Pasireotide (with active moiety).

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Drug Indications
Signifor is indicated for the treatment of adult patients with Cushing's disease who are unsuitable for surgery or whose surgery has failed. Signifor is indicated for the treatment of adult patients with acromegaly who are unsuitable for surgery or whose surgery has failed and whose condition is poorly controlled with other somatostatin analogs.

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Pasireotide is a six-membered isocyclic peptide composed of L-phenylglycyl, D-tryptophanyl, L-lysyl, O-benzyl-L-tyrosyl, L-phenylalanyl, and modified L-hydroxyproline residues linked in sequence. It is a somatostatin analog with pharmacological properties similar to the natural hormone somatostatin; (in its diaspartate form) used to treat Cushing's disease. It also has anti-tumor effects. It is a homocyclic peptide and a peptide hormone. It is the conjugate base of paretalin(2+). Paretalin is a synthetic, long-acting cyclic hexapeptide with somatostatin-like activity. It is marketed as diaspartate under the brand name Signifor for the treatment of Cushing's disease. Paretalin is a somatostatin analog. The mechanism of action of paretalin is as a somatostatin receptor agonist. Paretalin is a synthetic somatostatin polypeptide analog whose ability to inhibit the levels and activity of growth hormone, insulin, glucagon, and many other gastrointestinal peptides is similar to that of the natural hormone. Due to its longer half-life than somatostatin, paretalin can be used clinically to treat pituitary neuroendocrine tumors that secrete excessive growth hormone (leading to acromegaly) or adrenocorticotropic hormone (ACTH, leading to Cushing's disease). Paretalin has many side effects, including inhibition of gallbladder contraction and bile secretion; maintenance therapy can lead to gallstones, accompanied by elevated serum enzymes and bilirubin.
Paretoxin is a synthetic, long-acting cyclic peptide with somatostatin-like activity. Paretoxin activates multiple somatostatin receptors; in vitro studies have shown that its binding affinity for somatostatin receptors 1, 3, and 5 is significantly higher than that of octreotide, while its binding affinity for somatostatin receptor 2 is comparable. This drug inhibits the release of human growth hormone (HGH), glucagon, and insulin more effectively than somatostatin.
See also: Paretoxin diaspartate (its active fraction). Paretoxin pamoate (its active ingredient).
Indications
For the treatment of Cushing's disease, particularly in patients for whom pituitary surgery is unsuccessful or unsuitable.
FDA Label
Signifor is indicated for the treatment of adult patients with Cushing's disease who are unsuitable for or have failed surgery. Signifor is indicated for the treatment of adult patients with acromegaly who are unsuitable for or have failed surgery and whose condition is poorly controlled with other somatostatin analogues. Treatment of Acromegaly and Pituitary Gigantism
Excessive Pituitary ACTH Secretion, Pituitary-Dependent Cushing's Disease, Pituitary-Dependent Hyperadrenocortical Insufficiency
Mechanism of Action

Paritide activates multiple somatostatin receptors. In vitro experiments show that its binding affinity to somatostatin receptors 1, 3, and 5 is much higher than that of octreotide, while its binding affinity to somatostatin receptor 2 is comparable. Binding and activation of somatostatin receptors inhibits ACTH secretion, thereby reducing cortisol secretion in patients with Cushing's disease. Furthermore, this drug is more effective than somatostatin in inhibiting human growth hormone (HGH), glucagon, and insulin release.
Pharmacodynamics

Signifor® is a somatostatin analogue that reduces cortisol secretion levels in patients with Cushing's disease.

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Based on the structure-activity relationship, the functional group of growth hormone release inhibitory factor (SRIF) was transferred to a smaller cyclic hexapeptide template, and SOM230 (25) was discovered through a rational drug design method. SOM230 is a novel and stable cyclic hexapeptide somatostatin analog with unique high affinity binding to human somatostatin receptors (subtypes sst1-sst5). SOM230 has a potent and long-lasting inhibitory effect on the release of growth hormone and insulin-like growth factor-1, and is a promising candidate drug that is currently undergoing phase I clinical trials. [1] Parretide (SOM230) is a multi-receptor ligand somatostatin analog with high affinity for somatostatin receptor subtypes sst(1,2,3) and sst(5). Parretide can effectively inhibit the secretion of growth hormone (GH), insulin-like growth factor-I (IGF-I) and adrenocorticotropic hormone (ACTH), suggesting its potential efficacy in acromegaly and Cushing's disease. The long-term inhibitory effect of parretin on hormone secretion in animal models and the expression of multiple SST receptors in carcinoid tumors suggest that parretin may have a clinical advantage over octreotide in carcinoid tumor patients. In vitro experiments have shown that parretin has direct and indirect antitumor activities, including SST receptor-mediated apoptosis and anti-angiogenesis, suggesting that parretin may play a role in antitumor therapy. In summary, the preclinical evidence and preliminary results of clinical studies suggest that parretin is expected to become a new therapy for patients with symptoms of octreotide-resistant or refractory metastatic carcinoid tumors, new or persistent acromegaly, and that parretin may become the first targeted drug for Cushing's disease. [3] In summary, this study is the first to demonstrate the antisecretive, antiproliferative and pro-apoptotic effects of the novel long-acting somatostatin analog SOM230 in an insulinoma mouse model, and observed that it can improve the overall survival rate of mice. The enhanced activity spectrum of SOM230 is due to its enhanced activity against four of the five somatostatin receptor subtypes (sstr5, sstr2, sstr3 and sstr1). SOM230 treatment has significant clinical implications for unresectable or metastatic insulinomas, especially those that respond poorly to conventional therapies such as octreotide and/or diazoxide. SOM230 treatment may help alleviate symptoms and lead to tumor regression. We believe that this novel SOM230-targeted therapy strategy will benefit patients with pancreatic neuroendocrine tumors (PNETs). While these data strongly support the efficacy of parretin in this model, we also acknowledge that larger-scale studies are needed to advance this new approach to clinical trials. [2] We also investigated the progression of chronic inflammatory histopathological changes after long-term use of parretin. These changes were particularly pronounced after repeated intra-articular injections of the antigen. The current data clearly demonstrate that in this immune-mediated arthritis model, somatostatin receptor (SSTR) agonists can suppress not only acute inflammatory responses but also chronic inflammatory/destructive processes. Somatostatin receptor agonists have attracted much attention in clinical treatment due to their anti-inflammatory (comparable to dexamethasone) and analgesic effects. In fact, significant clinical improvement was observed after treatment with octreotide in a preliminary study of patients with rheumatoid arthritis (RA). Current observations suggest that parretoide and octreotide may have similar anti-inflammatory effects; however, parretoide is expected to be superior to octreotide in pain control in RA. In addition, somatostatin analogue therapy is considered relatively safe and well-tolerated. Moreover, both octreotide and parretoide have long-acting formulations available for long-term treatment; these formulations only require monthly administration and do not require daily subcutaneous injection. In summary, we provide evidence that the somatostatin receptor agonists octreotide and parretoide have potent anti-inflammatory and analgesic effects. We found that SSTR2 is an important target for the anti-inflammatory effects of somatostatin. Both SSTR2 and SSTR1 mediate analgesia. Regarding the clinical application of SSTR agonists, pan-SSTR agonists may be considered superior to selective SSTR2 agonists. [4]

C66H80N12O17

1313.41

1312.576

C, 60.36; H, 6.14; N, 12.80; O, 20.71

820232-50-6

396091-73-9;396091-76-2 (acetate);396091-79-5 (pamoate);820232-50-6 (diaspartate);

70788982

Typically exists as solid at room temperature

15

21

24

95

2070

9

O(C(NCCN)=O)[C@H]1CN2C([C@H](CC3C=CC=CC=3)NC([C@H](CC3C=CC(=CC=3)OCC3C=CC=CC=3)NC([C@H](CCCCN)NC([C@@H](CC3=CNC4C=CC=CC3=4)NC([C@H](C3C=CC=CC=3)NC([C@@H]2C1)=O)=O)=O)=O)=O)=O.OC([C@H](CC(=O)O)N)=O.OC([C@H](CC(=O)O)N)=O

NEEFMPSSNFRRNC-HQUONIRXSA-N

InChI=1S/C58H66N10O9.2C4H7NO4/c59-27-13-12-22-46-52(69)64-47(30-38-23-25-42(26-24-38)76-36-39-16-6-2-7-17-39)53(70)66-49(31-37-14-4-1-5-15-37)57(74)68-35-43(77-58(75)61-29-28-60)33-50(68)55(72)67-51(40-18-8-3-9-19-40)56(73)65-48(54(71)63-46)32-41-34-62-45-21-11-10-20-44(41)45;2*5-2(4(8)9)1-3(6)7/h1-11,14-21,23-26,34,43,46-51,62H,12-13,22,27-33,35-36,59-60H2,(H,61,75)(H,63,71)(H,64,69)(H,65,73)(H,66,70)(H,67,72);2*2H,1,5H2,(H,6,7)(H,8,9)/t43-,46+,47+,48-,49+,50+,51+;2*2-/m100/s1

(3S,6R,9S,12S,15S,19R,20aS)-6-((1H-indol-3-yl)methyl)-9-(4-aminobutyl)-15-benzyl-12-(4-(benzyloxy)benzyl)-1,4,7,10,13,16-hexaoxo-3-phenylicosahydropyrrolo[1,2-a][1,4,7,10,13,16]hexaazacyclooctadecin-19-yl (2-aminoethyl)carbamate bis(L-aspartate)

SOM 230; SOM-230; Pasireotide diaspartate; UNII-I4P76SY3N4; I4P76SY3N4; Pasireotide (as diaspartate); 820232-50-6; Cyclo((2R)-2-phenylglycyl-d-tryptophyl-l-lysyl-o-(phenylmethyl)-l-tyrosyl-l-phenylalanyl-(4R)-4-((((2-aminoethyl)amino)carbonyl)oxy)-l-prolyl), l-aspartate (1:2); SOM230; trade names: Signifor; Signifor LAR.

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.)