IC50: 0.45 μM (MAO-B)

Peak sodium current amplitude is lowered by Safinamide (1–300 µM) in a concentration-dependent manner. The IC50 value was 262 µM when currents were driven to a Vtest of +10 mV from a Vh of -110 mV. In rat cortical neurons, Safinamide exhibits an inhibitory action with a reduced IC50 value (8 µM) when the holding potential is depolarized to -53 mV[1].

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Safinamide, (S)-N2-{4-[(3-fluorobenzyl)oxy]benzyl}alaninamide methanesulfonate, which is in phase III clinical trials as an anti-Parkinson drug, and a library of alkanamidic analogues were prepared through an expeditious solid-phase synthesis and evaluated for their monoamine oxidase B (MAO-B) and monoamine oxidase A (MAO-A) inhibitory activity and selectivity. (S)-3-Chlorobenzyloxyalaninamide (8) and (S)-3-chlorobenzyloxyserinamide (13) derivatives proved to be more potent MAO-B inhibitors than Safinamide (IC50 = 33 and 43 nM, respectively, vs 98 nM) but with a lower MAO-B selectivity (SI = 3455 and 1967, respectively, vs 5918). The highest MAO-B inhibitory potency (IC50 = 17 nM) and a good selectivity (SI = 2941) were displayed by (R)-21, a tetrahydroisoquinoline analogue of Safinamide. Structure-affinity relationships and docking simulations pointed out strong negative steric effects of alpha-aminoamide side chains and para substituents of the benzyloxy groups and favorable hydrophobic interactions of meta substituents. The significantly diverse MAO-B affinities of a number of R and S alpha-aminoamide enantiomers, including the two rigid analogues (21) of safinamide, indicated likely enantioselective interactions at the enzymatic binding sites. [1]

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Sodium Channel Inhibition in Rat Cortical Neurons. [3]
Voltage pulses to +10 mV evoked fast inward sodium currents from cortical neurons, whose amplitude was dependent on the voltage of the conditioning pulse (see Materials and Methods). The conditioning voltage at which maximal (resting state, Vrest) and 50% maximal sodium current (half maximal inactivation state, Vhalf) could be evoked were −110 and −53 mV, respectively (Fig. 6A). According to the observed steady-state inactivation curve, the effects of Safinamide on sodium currents and voltage/state dependence of the block were tested at preconditioning potentials of −110 mV (Vrest) and −53 mV (Vhalf). As shown in Fig. 6B, Safinamide (1–300 µM) reduced the amplitude of the peak sodium currents (tonic block) in a concentration-dependent manner. When currents were stimulated to a Vtest of +10 mV from a Vh of −110 mV, the IC50 value was 262 µM. The inhibitory effect of safinamide was voltage-dependent since a significantly lower IC50 value (8 µM) was obtained when the holding potential was depolarized to −53 mV. Washout resulted in complete reversal of the inhibition. The affinity constant for the inactivated state of the sodium channel (Ki) was 4.1 µM.

When administered intraperitoneally (90 mg/kg, once daily for 14 days), safinamide significantly reduces the volume of cerebral infarction caused by MCAO in mice, as well as the neurological deficit, disruption of the blood-brain barrier (BBB), and expression of the tight junction proteins occludin and ZO-1[3]. In vivo, veratridine-induced GABA and Glu release is dose-dependently inhibited by safinamide (intraperitoneal injection; 5 mg/kg, 15 mg/kg, and 30 mg/kg). Safinamide blocks the effects of veratridine on GABA (treatment F1,8=4.04; time F8,64=3.76, time× treatment interaction F8,64 = 2.83) and Glu (treatment F1,8=1.31; time× treatment interaction F8,64=2.4) release at a dose of 30 mg/kg. In rats, safinamide completely inhibits veratridine-stimulated Glu release at doses of 5 and 15 mg/kg and reduces it slightly, but not significantly[3].

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Safinamide has been recently approved as an add-on to levodopa therapy for Parkinson disease. In addition to inhibiting monoamine oxidase type B, it blocks sodium channels and modulates glutamate (Glu) release in vitro. Since this property might contribute to the therapeutic action of the drug, we undertook the present study to investigate whether safinamide inhibits Glu release also in vivo and whether this effect is consistent across different brain areas and is selective for glutamatergic neurons. To this aim, in vivo microdialysis was used to monitor the spontaneous and veratridine-induced Glu and GABA release in the hippocampus and basal ganglia of naive, awake rats. Brain levels of safinamide were measured as well. To shed light on the mechanisms underlying the effect of safinamide, sodium currents were measured by patch-clamp recording in rat cortical neurons. Safinamide maximally inhibited the veratridine-induced Glu and GABA release in hippocampus at 15 mg/kg, which reached free brain concentrations of 1.89-1.37 µM. This dose attenuated veratridine-stimulated Glu (but not GABA) release in subthalamic nucleus, globus pallidus, and substantia nigra reticulata, but not in striatum. Safinamide was ineffective on spontaneous neurotransmitter release. In vitro, safinamide inhibited sodium channels, showing a greater affinity at depolarized (IC50 = 8 µM) than at resting (IC50 = 262 µM) potentials. We conclude that safinamide inhibits in vivo Glu release from stimulated nerve terminals, likely via blockade of sodium channels at subpopulations of neurons with specific firing patterns. These data are consistent with the anticonvulsant and antiparkinsonian actions of safinamide and provide support for the nondopaminergic mechanism of its action [3].

In Vitro Enzyme Activity Assay. The enzyme activities were assessed with a radioenzymatic assay using the selective substrates 14C-serotonin (5-HT) and 14C-phenylethylamine (PEA) for MAO-A and MAO-B, respectively. The mitochondrial pellet (500 μg protein) was resuspended in 200 μL of 0.1 M phosphate buffer, pH 7.40, and was added to 50 μL of the solution of the inhibitor (transformed to the methanesulfonate salt upon addition of a stoichiometric amount of 0.01 M methanesulfonic acid to the aqueous solution of the free base) or of buffer and incubated for 30 min at 37 °C (preincubation). Then the substrate in 50 μL of buffer (5 μM 14C-5-HT or 0.5 μM 14C-PEA) was added and the assay mixture was incubated at 37 °C for 30 min (5-HT) or for 10 min (PEA). [1]
The reaction was stopped by adding 0.2 mL of HCl or perchloric acid for 5-HT or PEA, respectively. After centrifugation, the acidic radioactive metabolites were extracted with 3 mL of diethyl ether (for 5-HT) or toluene (for PEA) and the radioactivity of the organic phase was measured by liquid scintillation spectrometry at 90% efficiency. [1]
The enzymatic activity was expressed as nanomoles of substrate transformed per milligram of protein per minute (nmol mg-1 min-1). [1]
The drug inhibition curves were obtained from five to eight different concentrations (10-10−10-5 M), each in duplicate, and the IC50 was determined using nonlinear regression analysis (GraphPad best-fitting computer program). For very low active inhibitors, the percent of enzyme inhibition was determined in duplicate at the concentrations indicated in Table.1.

Whole-Cell Patch-Clamp Recording. [3]
The experiments were carried out according to standard whole-cell patch-clamp recording techniques (Hamill et al., 1981) at room temperature (25°C). Neuronal cells were continuously superfused with an extracellular solution containing (in millimolars) NaCl (60), choline chloride (60), CaCl2 (1.3), MgCl2 (2), CdCl2 (0.4), NiCl2 (0.3), TEACl (20), glucose (10), and HEPES (10). Patch pipettes were pulled using a Sutter P-87 electrode puller and filled with an internal solution consisting of (in millimolars): CsF (65), CsCl (65), NaCl (10), CaCl2 (1.3), MgCl2 (2), EGTA (10), HEPES (10), and MgATP (1). Patch electrodes had a tip resistance of 2–3 MΩ. Membrane currents were recorded and filtered at 5 kHz using an Axopatch 200B amplifier, and data were digitized using an Axon Digidata 1322A. Voltage command protocols and data acquisitions were controlled using Axon pClamp8 software. Measuring and reference electrodes were AgCl-Ag electrodes. Access resistance ranged from 5 to 10 MΩ; linear leakage and capacitative currents were eliminated using a P/4 leak subtraction protocol. Safinamide (20 mM stock solution in distilled water) was diluted in external solution and applied for 2 minutes to reach an equilibrium response.

Animal/Disease Models: Focal cerebral ischemia C57/BL6 male mouse Model[3]
Doses: 90 mg/kg
Route of Administration: intraperitoneal (ip)injection; one time/day; 14 days
Experimental Results: Dramatically diminished infarction volume in brain areas.

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\n\nExperimental Protocols and Design. [3]
\nNinety-five rats were used for the microdialysis experiments, 84 for the study of veratridine-stimulated neurotransmitter release and 11 for the study of spontaneous release. The experimental protocols were approved by the Italian Ministry of Health (licenses 170/2013B and 714/2016-PR-B). As for the design of the experiments (Fig. 1, C and D and Fig. 2), each rat was randomized to saline/veratridine or Safinamide/veratridine (0.5, 5, or 15 mg/kg, Fig. 1, C and D; 5 or 15 mg/kg, Fig. 2) in the first and second microdialysis sessions, ensuring that no rat received the same treatment in the two sessions. Rats underwent two microdialysis sessions (i.e., at 24 and 48 hours after probe implantation), after which they were sacrificed with an isoflurane overdose, and placement of the probes was verified histologically. For study of veratridine-stimulated release (Fig. 1, A and B, 3, 4, and 5), each animal implanted with a single microdialysis probe was randomized to saline/veratridine or Safinamide/veratridine (30 mg/kg, Fig. 1, A and B; 15 mg/kg, Figs. 3–5) in the first microdialysis session, and treatments crossed in the second session. For the study on spontaneous Glu and GABA release, rats implanted with one probe in STN and another in the contralateral SNr were randomized to saline or veratridine 15 mg/kg in the first microdialysis session, and treatments crossed in the second session. Overall, seven animals were discarded for probe misplacement or probe clogs during microdialysis.\n

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\nIn Vivo Microdialysis. [3]
\nIntracerebral microdialysis was performed as previously described (Morari et al., 1996; Paolone et al., 2015). One probe of concentric design was stereotaxically implanted under isoflurane anesthesia in five different brain regions according to the following coordinates (in millimeters) from the bregma and the dural surface (Paxinos and Watson, 1986): hippocampus (1-mm dialyzing membrane, antero-posterior (AP) −3.14, medio-lateral (ML) ± 1.8, dorso-ventral (DV) −4.2.), STN (1-mm dialyzing membrane, AP −3.7, ML ± 2.5, DV −8.6), SNr (1-mm dialyzing membrane, AP −5.5, ML ± 2.2, DV −8.3), DLS (3-mm dialyzing membrane, AP +1.0, ML ± 3.5, DV −6.0) and GP (2-mm dialyzing membrane, AP −1.3, ML ± 3.3, DV −6.5). When veratridine-stimulated neurotransmitter release was studied, each animal was implanted with one probe at the time. Conversely, when spontaneous neurotransmitter release was studied, each animal was implanted with two probes at the same time, one in the STN and another in the contralateral SNr. Probes were secured to the skull with dental cement. The wound was infiltrated with local anesthetic (lidocaine 2%) before surgery completion. Twenty-four hours after surgery, the probes were perfused with a modified Ringer’s solution (1.2 mM CaCl2, 2.7 mM KCl, 148 mM NaCl, and 0.85 mM MgCl2) at a flow rate of 3.0 μl/min, and sample collection (every 20 minutes) began after 6 hours of rinsing. At least four baseline samples were collected before systemic (i.p.) administration of saline or Safinamide. Thirty minutes later, veratridine (10 μM) was perfused for 30 minutes through the probe by reverse dialysis; at the end of veratridine perfusion, sample collection was continued for 80 minutes.\n

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\nBrain Pharmacokinetic Analysis. [3]
\nTwenty-seven rats were used for pharmacokinetic analysis.Safinamide was administered at three dose levels (5, 15, and 30 mg/kg, i.p.), and brains were removed 40, 60, and 80 minutes later to match the veratridine perfusion time in the microdialysis study. Brain samples were homogenized by sonication; after protein precipitation, the total Safinamide concentration was measured by HPLC-tandem mass spectrometry on a Sciex API4000 mass spectrometer (AB Sciex, Framingham, MA). Samples (5 µl) were injected using a CTC analytics HTS Pal autosampler (Zwingen, Switzerland) onto a Synergi MAX-RP 30 ×2.0 mm, 4-µm column at an eluent flow rate of 1.5 ml/min. Analytes were eluted using a high-pressure linear gradient program by an HP1100 binary HPLC system. To calculate the free brain concentration, the fraction of unbound Safinamide in the brain (fu,b) was determined by in vitro equilibrium dialysis (Summerfield et al., 2007). The fu,b percent was 3.27.\n

Absorption, Distribution and Excretion
Absorption is rapid, with peak plasma concentrations reached within 2 to 4 hours, and a total bioavailability of 95%. Food prolongs the absorption rate but does not affect the extent of safinamide absorption. 76% is excreted via the kidneys, and 1.5% via feces. 1.8 L/kg. The mean total oral plasma clearance (including parent safinamide and its metabolites) is only 17.53 ± 2.71 mL/h × kg. Metabolism/Metabolites The main step is mediated by an unidentified amidase to produce safinamide acid. It is also metabolized to O-debenzylamidamide and N-dealkylamine. The N-dealkylamine is subsequently oxidized to a carboxylic acid, which is ultimately glucuronidated. The dealkylation reaction is mediated by cytochrome P450 (CYP), particularly CYP3A4. Safinamide acid binds to organic anion transporter 3 (OAT3), but the clinical significance of this interaction has not been determined. Safenamide also binds transiently to ABCG2. Preliminary studies have not found affinity for other transport proteins.

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Biological half-life
22 hours

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Safenamide brain concentration. [3]
In another group of rats, the brain concentration of safenamide was measured at 40, 60 and 80 minutes after administration of 5, 15 or 30 mg/kg safenamide. The free brain concentration calculated by taking into account the binding of safenamide in brain tissue was dose-dependent. At all time points, the brain concentration was highest in the 30 mg/kg dose group and lowest in the 5 mg/kg dose group (Table 1). In addition, a gradual linear decrease was observed from the first time point to the last time point in all dose groups. During veratrine perfusion (100–120 minutes), the concentrations of free safenamide in brain tissue ranged from 0.70–0.44, 1.89–1.70, and 4.77–3.04 µM, respectively, in the 5, 15, and 30 mg/kg dose groups.

Hepatotoxicity

It has been reported that a small number of patients taking safenamide long-term may experience elevated serum enzymes, but these abnormalities are usually mild and resolve spontaneously, and the incidence is generally no higher than that of placebo or control drugs. Safenamide has not been reported to be associated with cases of acute liver injury, but such cases have been reported with nonspecific monoamine oxidase inhibitors.
Probability Score: E (Unlikely to cause clinically significant liver injury).

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the use of safenamide during lactation. Due to the hepatotoxicity of this drug in lactating rat pups, the manufacturer recommends that it be contraindicated in lactating 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.

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Protein Binding

88–90%

[1]. Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase. J Med Chem, 2007, 50(20), 4909-4916.

[2]. Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology. 2006 Oct 10;67(7 Suppl 2):S18-23.

[3]. Safinamide Differentially Modulates In Vivo Glutamate and GABA Release in the Rat Hippocampus and Basal Ganglia.J Pharmacol Exp Ther. 2018 Feb;364(2):198-206.

(2R)-2-[[4-[(3-fluorophenyl)methoxy]phenyl]methylamino]propionamide is an amino acid amide. Safenamide is also an amino acid amide. Safenamide is used to treat Parkinson's disease. It was approved in Europe in February 2015 and in the United States on March 21, 2017. Safenamide is a monoamine oxidase type B inhibitor. The mechanism of action of safenamide is as a monoamine oxidase type B inhibitor and a breast cancer resistance protein inhibitor. Safenamide is a monoamine oxidase inhibitor used in combination with levodopa and carbidopa as adjunctive therapy for the treatment of Parkinson's disease. The incidence of serum enzyme elevation during safenamide treatment is low, but it has not been found to be associated with clinically significant cases of acute liver injury. See also: Safenamide mesylate (active ingredient). Safenamide is indicated for use as adjunctive therapy to levodopa and in combination with other medications for the treatment of Parkinson's disease. Safinamide (Xadago) is indicated for the treatment of adult patients with idiopathic Parkinson's disease (PD) as adjunctive therapy to a stable dose of levodopa (L-dopa). It can be used alone or in combination with other PD medications for patients with fluctuating disease in the middle to late stages. Mechanism of Action: Safinamide is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible MAO-B inhibition with voltage-dependent Na+ and Ca2+ channel blockade and glutamate release inhibition. Safinamide has neuroprotective and neuroreparative effects in MPTP-treated mouse and rat erythrocyanine models and gerbil ischemia models. Safinamide, (S)-N2-{4-[(3-fluorobenzyl)oxy]benzyl}alanine methanesulfonate, is currently in Phase III clinical trials for its use as an anti-Parkinson's disease drug. A series of alkanoamide analogs were prepared using a rapid solid-phase synthesis method, and their inhibitory activities and selectivity against monoamine oxidase B (MAO-B) and monoamine oxidase A (MAO-A) were evaluated. The MAO-B inhibitory activities of the derivatives of (S)-3-chlorobenzyloxyalanine (8) and (S)-3-chlorobenzyloxyserine (13) were stronger than those of safinamide (IC50 values of 33 nM and 43 nM, respectively, compared to 98 nM for safinamide), but their MAO-B selectivity was lower (SI values of 3455 and 1967, respectively, compared to 5918 for safinamide). The tetrahydroisoquinoline analogue (R)-21 of safinamide exhibited the highest MAO-B inhibitory activity (IC50 = 17 nM) and good selectivity (SI = 2941). Structure-affinity relationships and molecular docking simulations showed that the para-substituents of the α-aminoamide side chain and benzyloxy group had strong negative steric hindrance, while the meta-substituents had favorable hydrophobic interactions. The significant differences in the affinity of various R and S α-aminoamide enantiomers, including two rigid analogues of safinamide (21), for MAO-B suggest that there may be enantioselective interactions at the enzyme binding site. [1] The ideal treatment goal for Parkinson's disease (PD) is to relieve symptoms and slow disease progression. Among all drugs, levodopa remains the most effective drug for relieving symptoms, but the medical need for neuroprotective drugs remains unmet. Safinamide is currently in a phase III clinical trial for the treatment of PD and is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective and reversible inhibition of MAO-B with blocking effects on voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safenamide showed neuroprotective and neuroreparative effects in MPTP-treated mice, rat erythrocyanine models and gerbil ischemia models. Safenamide enhanced levodopa-mediated DA level elevation (in DA-depleted mice) and reversed the weakening of motor response after long-term levodopa treatment in 6-OHDA-damaged rats. Safenamide has good bioavailability and linear pharmacokinetics, making it suitable for once-daily administration. Therefore, safenamide can be used to treat Parkinson's disease to reduce the dosage of levodopa, and it is also a valuable therapeutic agent that can be used to test its disease improvement potential. [2]

C17H19FN2O2

302.34

302.143

C, 67.53; H, 6.33; F, 6.28; N, 9.27; O, 10.58

174756-44-6

133865-89-1; 202825-46-5 (mesylate)

5487407

White to off-white solid powder

3.908

2

4

7

22

346

1

FC1=CC=CC(=C1)COC1C=CC(=CC=1)CNC(C(N)=O)C

NEMGRZFTLSKBAP-GFCCVEGCSA-N

InChI=1S/C17H19FN2O2/c1-12(17(19)21)20-10-13-5-7-16(8-6-13)22-11-14-3-2-4-15(18)9-14/h2-9,12,20H,10-11H2,1H3,(H2,19,21)/t12-/m1/s1

(2R)-2-[[4-[(3-fluorophenyl)methoxy]phenyl]methylamino]propanamide

FCE 28073; 174756-44-6; (2R)-2-[[4-[(3-fluorophenyl)methoxy]phenyl]methylamino]propanamide; (R)-Safinamide; CHEMBL82327; (R)-2-((4-((3-Fluorobenzyl)oxy)benzyl)amino)propanamide; Propanamide, 2-[[[4-[(3-fluorophenyl)methoxy]phenyl]methyl]amino]-, (2R)-; (R)-2-[[4-[(3-Fluorobenzyl)oxy]benzyl]amino]propanamide; PROPANAMIDE, 2-(((4-((3-FLUOROPHENYL)METHOXY)PHENYL)METHYL)AMINO)-, (2R)-; (R)-EMD 1195686

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ≥ 125 mg/mL (413.44 mM)

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.)