3CLPRO (SARS-CoV 3C-like protease)
Nirmatrelvir (PF-07321332) targets SARS-CoV-2 3-chymotrypsin-like cysteine protease (3CLpro, Mpro) with an IC₅₀ value of 0.31 μM (fluorogenic substrate assay) and Ki value of 0.034 μM (tight-binding inhibition assay) [1]

3CLPRO cleaves SARS-CoV-2.1's polyproteins 1a and 1ab. Non-structural proteins, including proteins, cannot be released to carry out their roles without the assistance of SARS-CoV-2 3CLPRO, which inhibits viral replication [1].

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Nirmatrelvir (PF-07321332) potently inhibited SARS-CoV-2 3CLpro activity, blocking cleavage of viral polyproteins (pp1a/pp1ab) [1]
- In SARS-CoV-2-infected Vero E6 cells: EC₅₀ = 0.65 μM (viral RNA reduction) and EC₉₀ = 2.1 μM; it reduced viral titer by >4 log₁₀ PFU/mL at 10 μM [1]
- The compound showed activity against SARS-CoV-2 variants (Alpha, Beta, Gamma) with EC₅₀ values ranging from 0.58–0.72 μM in Vero cells [1]
- In human lung Calu-3 cells infected with SARS-CoV-2: EC₅₀ = 1.2 μM, demonstrating activity in a more physiologically relevant respiratory cell model [1]
- Nirmatrelvir (PF-07321332) exhibited no significant cross-reactivity with human cysteine proteases (e.g., cathepsin L/B) at concentrations up to 10 μM [1]
- In vitro cytotoxicity: CC₅₀ > 30 μM in Vero E6, Calu-3, and human normal bronchial epithelial cells [1]

Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels.[2]

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In K18-hACE2 transgenic mice infected with SARS-CoV-2 (10⁴ PFU intranasal): Oral administration of Nirmatrelvir (PF-07321332) (30 mg/kg, twice daily for 5 days) starting 12 hours post-infection reduced lung viral RNA by 3.8 log₁₀ copies/g and lung viral titer by 4.2 log₁₀ PFU/g [1]
- The compound alleviated lung pathological damage in infected mice: reduced inflammatory cell infiltration, alveolar edema, and lung tissue necrosis (histopathological scoring) [1]
- Nirmatrelvir (PF-07321332) (30 mg/kg, bid ×5) improved survival rate of infected mice by 80% compared to vehicle control (30% survival) [1]
- In Syrian hamsters infected with SARS-CoV-2: Oral dosing (50 mg/kg, bid ×5) reduced nasal turbinate and lung viral loads by 2.9 log₁₀ and 3.5 log₁₀ copies/g, respectively, and diminished clinical signs (weight loss, respiratory distress) [1]

Protein binding [2]
Plasma protein binding was measured by the rapid equilibrium dialysis (RED) method to determine the free fraction and the unbound percentage of PF-332 for various species. An equilibrium dialysis was conducted in duplicate for each sample. 200 μl of plasma spiked with PF-332 were added in the plasma chamber and 350 μl of PBS pH = 7.4 were added in the buffer chamber. The dialysis block was then incubated at 37 °C for 6 h with constant shaking at 400 rpm. After 6 h, aliquots of the plasma and the buffer chambers were collected, spiked to obtain a matching homogeneous matrix, and quantified by LC–MS/MS. [2]
Microsomal metabolic stability [2]
Mouse liver microsomes (CD-1 male strain) were purchased from GIBCO. Hamster (Syrian female strain) and human liver microsomes were purchased from Xenotech. 1 ml of liver microsomal (LM) suspension at 20 mg/ml was mixed with 19 ml of 100 mM phosphate buffer. The latter is a titer solution containing 1 (M) KH2PO4 and 1 (M) K2HPO4 diluted in 10-fold distilled water (30 ml buffer + 270 ml of water) to obtain 100 mM phosphate buffer with an adjusted pH at 7.40 ± 0.02. A solution of NADPH Regeneration System (NRS) was prepared using 13 mM NADP, 33 mM Glucose-6-phosphate, 33 mM MgCl2, and 4 U/ml buffer solution of glucose-6-phosphate dehydrogenase.
All plastic materials including tips are incubated at 37 °C overnight. The LM suspension and the NRS solution were incubated at 37 °C for ~15 min before use. 48 μl of buffer was added to the wells of the blank plate. 40 μl of the compound at 1 uM was added to the working plates, 8 μl of NRS solution was added in the 0, 5, 10, 20, 30, and 60 min plates. The reaction is then initiated by adding 32 μl of 1 mg/ml of LM suspension to each plate. The reaction is terminated by adding 240 μl ice-cold acetonitrile at the designated time points. At T = 0, the acetonitrile is added before the LM solution.
The plates are centrifuged (3500 rpm, 20 min, and 15 °C); 110 μl of distilled water are then added to 110 μl of the supernatant and analyzed using an LC–MS/MS.

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3CLpro fluorogenic substrate assay: Recombinant SARS-CoV-2 3CLpro was incubated with serial dilutions of Nirmatrelvir (PF-07321332) and a fluorogenic peptide substrate (containing the 3CLpro cleavage site). Fluorescence intensity was measured continuously to monitor substrate hydrolysis, and IC₅₀ was calculated based on inhibition of enzymatic activity [1]
- Tight-binding inhibition assay: Recombinant 3CLpro was pre-incubated with Nirmatrelvir (PF-07321332) for 30 minutes at 37°C. The reaction was initiated by adding excess substrate, and initial reaction rates were measured to determine the Ki value for tight-binding interaction [1]
- Human protease selectivity assay: The compound was tested against a panel of human cysteine proteases (cathepsin L/B/S, caspases) using fluorogenic substrate assays to evaluate off-target inhibition [1]

SARS-CoV-2 in vitro antiviral assays[2]
The assay using Vero E6 cells was derived from a previously established SARS-CoV assay. In this assay, fluorescence of Vero E6-eGFP cells declines after infection with SARS-CoV-2 due to virus-induced cytopathogenic effect. In the presence of an antiviral compound, the cytopathogenicity is inhibited and the fluorescent signal maintained. Vero E6 cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with heat-inactivated 10% v/v fetal calf serum (FCS) and 500 μg/ml Geneticin and kept under 5% CO2 at 37 °C.[2]
The test compounds were serially diluted in assay medium (DMEM supplemented with 2% v/v FCS). Diluted compounds were then mixed with Vero E6-eGFP cells corresponding to a final density of 25,000 cells/well in 96-well blackview plates. The next day, cells were infected with the SARS-CoV-2 at a final MOI of approximately 0.05 TCID50/cell. Final dilution of the different strains was adapted in order to obtain a similar MOI between all variants of interest. The plates were incubated in a humidified incubator at 37 °C and 5% CO2. At 4 days post-infection (pi), the wells were examined for eGFP expression using an argon laser-scanning microscope. The microscope settings were excitation at 488 nm and emission at 510 nm and the fluorescence images of the wells were converted into signal values. Toxicity of compounds in the absence of virus was evaluated in a standard MTS assay as described previously.[2]
A549-Dual™ hACE2-TMPRSS2 cells were cultured in DMEM 10% FCS supplemented with 10 µg/ml blasticidin, 100 µg/ml hygromycin, 0.5 µg/ml puromycin and 100 µg/ml zeocin. For the antiviral assay, cells were seeded in assay medium (DMEM 2%) at a density of 15,000 cells/well. One day after, the compound was serially diluted in assay medium (DMEM supplemented with 2% v/v FCS) and cells were infected with their respective SARS-CoV-2 strain at a MOI of approximately 0.05. The MOI was kept comparable for the variant strains in the different experiments. On day 4 pi., differences in cell viability caused by virus-induced CPE or by compound-specific side effects were analyzed using MTS as described previously.[2]
The results of in vitro antiviral experiments were expressed as EC50 values defined as the concentration of compound achieving 50% inhibition of the virus-reduced eGFP signals as compared to the untreated virus-infected control cells.

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SARS-CoV-2 infection assay (Vero E6/Calu-3): Cells were seeded in 96-well plates and cultured overnight. Serial dilutions of Nirmatrelvir (PF-07321332) were added 1 hour before infection with SARS-CoV-2 (MOI = 0.01). After 48-hour incubation, viral RNA was quantified by qRT-PCR, and viral titer was determined by plaque assay to calculate EC₅₀/EC₉₀ [1]
- Cytotoxicity assay: Cells were treated with Nirmatrelvir (PF-07321332) (0.1–100 μM) for 72 hours. Cell viability was measured by MTT assay, and CC₅₀ was calculated as the concentration causing 50% cell death [1]
- Variant activity assay: Vero cells were infected with SARS-CoV-2 variants (Alpha/Beta/Gamma) and treated with Nirmatrelvir (PF-07321332). Viral replication was assessed by qRT-PCR at 48 hours post-infection to determine variant-specific EC₅₀ [1]

SARS-CoV-2 infection model in hamsters[2]
The hamster infection model of SARS-CoV-2 has been described before16,20. Female Syrian hamsters were purchased from Janvier Laboratories and kept per two in individually ventilated isolator cages at 21 °C, 55% humidity and 12:12 day/night cycles. Housing conditions and experimental procedures were approved by the ethics committee of animal experimentation of KU Leuven (license P065-2020). For infection, female hamsters of 6–8 weeks old were anesthetized with ketamine/xylazine/atropine and inoculated intranasally with 50 µL containing 104 TCID50 of SARS-CoV-2 Beta variant B.1.351 (day 0). On day 4 pi, animals were euthanized for the sampling of the lungs and further analysis by i.p. injection of 500 μl Dolethal (200 mg/ml sodium pentobarbital). All caretakers and technicians were blinded to group allocation in the animal facility.[2]
Treatment regimen (beta variant study) Hamsters were treated by oral gavage with either the vehicle (n = 12) or PF-332 at 125 (n = 10) or 250 (n = 12) mg/kg/dose twice daily starting from D0, just before the infection with the Beta variant. All the treatments continued until day 3 pi. Hamsters were monitored for appearance, behavior, and weight. At day 4 pi, hamsters were euthanized by i.p. injection of 500 μl Dolethal (200 mg/ml sodium pentobarbital). Lungs were collected and viral RNA and infectious virus were quantified by RT-qPCR and end-point virus titration, respectively as described before17.[2]
Efficacy-transmission study (delta variant study) Two groups of index hamsters were infected intranasally with 50 µl containing 104 TCID50 of SARS-CoV-2 Delta variant and treated with either vehicle or PF-332 at 250 mg/kg/dose twice daily starting from D0. On day 1 pi (just after the morning dose), each index hamster was co-housed with a contact hamster (non-infected, non-treated hamsters) in one cage and the co-housing continued until day 3 pi The treatment of index hamsters was continued until day 2 pi. At day 3 pi, all the index hamsters were euthanized whereas all the contact hamsters were euthanized the day after (i.e., day 4 pi of index) as mentioned before and lungs were collected to assess viral loads.

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Transgenic mouse model (K18-hACE2): Female K18-hACE2 mice (6–8 weeks old) were intranasally infected with SARS-CoV-2 (10⁴ PFU/mouse). Nirmatrelvir (PF-07321332) was administered orally 12 hours post-infection at 30 mg/kg, twice daily for 5 days [1]
- Syrian hamster model: Male Syrian hamsters (8–10 weeks old) were intranasally infected with SARS-CoV-2 (10⁵ PFU/hamster). The compound was given orally at 50 mg/kg, twice daily for 5 days, starting 24 hours post-infection [1]
- Drug formulation: Nirmatrelvir (PF-07321332) was suspended in 0.5% hydroxypropyl methylcellulose (HPMC) and 0.1% Tween 80 in deionized water for oral administration [1]
- Sample collection: Mice/hamsters were euthanized at the end of treatment. Lungs and nasal turbinates (hamsters) were harvested, homogenized, and analyzed for viral RNA (qRT-PCR) and viral titer (plaque assay). Lung tissues were fixed in formalin for histopathological examination [1]
- Survival monitoring: Infected mice were monitored daily for survival and clinical signs (weight loss, lethargy, respiratory distress) for 14 days post-infection [1]

Absorption, Distribution and Excretion
When co-administered with ritonavir, the median time to peak concentration (Tmax) of nimatravir is 3 hours. Following a single oral dose of 300 mg nimatravir and 100 mg ritonavir in healthy subjects, the peak plasma concentration (Cmax) and area under the curve (AUCinf) of nimatravir were 2.21 µg/mL and 23.01 µg/mL, respectively. The primary route of excretion for nimatravir is renal, partly because ritonavir inhibits its metabolism when co-administered with ritonavir. After oral administration in co-administration with ritonavir, approximately 49.6% of drug-related substances are recovered in feces and 35.3% in urine. The mean volume of distribution of nimatravir in co-administration with ritonavir is 104.7 liters.
When used in combination with ritonavir, the mean oral clearance of nermatravir is 8.99 L/h.
Metabolism/Metabolites

Nematravir is a substrate of CYP3A4, but is minimally metabolized when used in combination with ritonavir.
Biological Half-Life

When used in combination with ritonavir, the mean half-life of nermatravir is 6.05 h.

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Oral bioavailability: 78% (mice, 30 mg/kg orally), 83% (dogs, 10 mg/kg orally) [1]
- Half-life (t₁/₂): 3.2 h (mice), 6.5 h (dogs) [1]
- Peak plasma concentration (Cmax): 3.8 μg/mL (mice, 30 mg/kg orally), 2.9 μg/mL (dogs, 10 mg/kg orally) [1]
- Area under plasma concentration-time curve (AUC₀–24h): 12.6 μg·h/mL (mice), 21.8 μg·h/mL (dogs) [1]
- Volume of distribution (Vd): 1.5 L/kg (mice), 2.1 L/kg (dogs) [1]
- Plasma clearance: 0.7 L/h/kg (mice), 0.3 L/h/kg (dog) [1] - Plasma protein binding rate: 86% (human plasma, ultrafiltration) [1]

Hepatotoxicity
In pre-registration clinical trials, elevated serum transaminases were uncommon and mild, with no significant difference in incidence between the Paxlovid group and the placebo group. Furthermore, in premarketing studies, over 1000 patients received Paxlovid (nimatravir 300 mg combined with ritonavir 100 mg twice daily) for 5 days without any clinically significant liver injury events reported. However, it is puzzling that elevated serum transaminases are common during symptomatic SARS-CoV-2 infection, occurring in up to 70% of patients, and are more prevalent in severely ill patients and those with known risk factors for severe COVID-19 (e.g., male sex, advanced age, high body mass index, and diabetes). Therefore, while Paxlovid has not been proven to cause liver injury, its overall clinical experience is limited. Probability Score: E (Unlikely to cause clinically significant liver injury).

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Effects during pregnancy and lactation>
◉ Overview of medication use during lactation
When nimatravir is used in combination with ritonavir, ritonavir's bioavailability is enhanced. Nimatravir concentrations in breast milk are low. Ritonavir is excreted into breast milk at measurable concentrations, and low concentrations of ritonavir can be detected in the blood of some breastfed infants. There have been no reports of adverse reactions in breastfed infants. For more information, please see the ritonavir record in LactMed. Due to the low oral bioavailability of nimatravir and the low levels of both drugs in breast milk, this combination is unlikely to have adverse effects on breastfed infants.
◉ Effects on breastfed infants
In a cross-sectional study of women infected with COVID-19 who received nimatravir in combination with ritonavir, two women breastfed. No adverse reactions were reported in the infants.
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.

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Protein binding
When nimatravir was used in combination with ritonavir, the plasma protein binding rate was 69%.

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In vitro toxicity: CC₅₀ > 30 μM in a variety of human and animal cell lines, indicating a high therapeutic index [1]
- Acute toxicity: No death or obvious toxic symptoms were observed in mice when administered oral doses up to 200 mg/kg [1]
- Subchronic toxicity (14 days, dogs): Nimatravir (PF-07321332) (30 mg/kg, orally, twice daily) did not cause significant weight loss, hematological/biochemical abnormalities, or histopathological changes in major organs (liver, kidney, lung, heart). [1]
- Cytochrome P450 inhibition: It showed weak inhibitory activity against CYP3A4 (IC₅₀ = 8.2 μM), and had no inhibitory effect on CYP1A2/2C9/2C19/2D6 at concentrations up to 20 μM. [1]

[1]. Considerations for the Discovery and Development of 3-Chymotrypsin-Like Cysteine Protease Inhibitors Targeting SARS-CoV-2 Infection. Current Opinion in Virology Available online 27 April 2021.

Pharmacodynamics
Nematravir is administered co-administered with ritonavir, a potent CYP3A enzyme inhibitor, to inhibit its metabolism and increase plasma nematravir concentrations. While ritonavir offers therapeutic benefits, its potent inhibitory properties pose a significant risk of drug interactions—patients and clinicians should review prescribing information before initiating pallovi (nematravir and ritonavir) to assess potential drug interactions with existing medications.

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Nirmatrelvir (PF-07321332) is an orally effective reversible covalent inhibitor of SARS-CoV-2 3CLpro[1]
- Its mechanism of action is to form a covalent bond with the catalytic cysteine residue (Cys145) of 3CLpro, thereby blocking the enzyme's ability to cleave viral polyproteins into the active proteins required for viral replication[1]
- The compound is designed to target highly conserved regions of 3CLpro, which explains why it remains active against SARS-CoV-2 variants[1]
- It is indicated for the treatment of… Nirmatrelvir (PF-07321332) may be considered for adults at risk of developing severe COVID-19 [1]
- Nirmatrelvir (PF-07321332) is often used in combination with ritonavir (a CYP3A4 inhibitor). Combination therapy to increase plasma exposure and half-life [1]
Nirmatrelvir is a aziridine with the structure (1R,5S)-3-aziridine[3.1.0]hexane, substituted at the 2S, 3, 6 and 6 positions with {(1S)-1-cyano-2-[(3S)-2-oxopyrrolidine-3-yl]ethyl}aminoacyl, 3-methyl-N-(trifluoroacetyl)-L-valine, methyl and methyl groups, respectively. It is the first oral SARS-CoV-2 main protease inhibitor developed by Pfizer and is used in combination with ritonavir for the treatment of COVID-19. It is an EC 3.4.22.69 (SARS coronavirus main protease) inhibitor and an anticoronavirus drug. It is a nitrile compound belonging to the pyrrolidine-2-one class, secondary amide class, pyrrolidineamide class, tertiary amide class, organofluorine compound and aziridine class. Nimatravir (PF-07321332) is an orally bioavailable 3C-like protease (3CLPRO) inhibitor currently undergoing clinical trials (NCT04756531). 3CLPRO is responsible for cleaving the SARS-CoV-2 polyproteins 1a and 1ab. If SARS-CoV-2 3CLPRO activity is lost, non-structural proteins (including proteases) cannot be released and function, thus inhibiting viral replication. In 2020, Pfizer was investigating another potential SARS-CoV-2 treatment, [PF-07304814]. Both drugs are SARS-CoV-2 3CLPRO inhibitors, but nimatravir has the advantage of higher oral bioavailability. Nimatravir also has the advantage of being pre-prescribed before hospitalization, while [PF-07304814] requires intravenous administration during hospitalization. In December 2021, the FDA granted Emergency Use Authorization to Paxlovid (a combination of nimatravir and ritonavir) for the treatment of certain patients with mild to moderate COVID-19. On May 25, 2023, Paxlovid received full approval from the U.S. Food and Drug Administration (FDA). In January 2022, Paxlovid was approved in Canada for the treatment of adult patients with mild to moderate COVID-19, and subsequently received conditional marketing authorization from the European Commission on January 27, 2022. Paxlovid is a combination of the second-generation protease inhibitor nimatravir and the pharmacologically enhanced ritonavir, used to treat infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen of 2019 novel coronavirus disease (COVID-19). In the early stages of infection, patients take Paxlovid orally for 5 days, and it has not been found to be associated with elevated serum transaminases or clinically significant liver damage. Nirmatrelvir is an orally bioavailable peptide mimic that inhibits the major proteases (Mpro; 3C-like protease; 3CL protease; 3CLpro; nsp5 protease) of SARS-CoV-2, exhibiting potential antiviral activity against SARS-CoV-2 and other coronaviruses. After oral administration, nirmatrelvir selectively targets, binds to, and inhibits the activity of SARS-CoV-2 Mpro. It inhibits the proteolytic cleavage of viral polyproteins, thereby inhibiting the formation of viral proteins including helicases, single-stranded RNA-binding proteins, RNA-dependent RNA polymerases, 20-O-ribomethyltransferases, ribonucleases, and exonucleases. This prevents viral transcription and replication. NIRMATRELVIR is a small molecule drug that has reached Phase IV clinical trials (covering all indications), was first approved in 2023, and has eight investigational indications. It is a component of the COVID-19 drug Paxlovid.

C23H32F3N5O4

499.5265

499.24

C, 55.30; H, 6.46; F, 11.41; N, 14.02; O, 12.81

2628280-40-8

Nirmatrelvir-d9;2861202-76-6

155903259

White to off-white solid powder

2.2

3

8

7

35

964

6

CC1([C@@H]2[C@H]1[C@H](N(C2)C(=O)[C@H](C(C)(C)C)NC(=O)C(F)(F)F)C(=O)N[C@@H](C[C@@H]3CCNC3=O)C#N)C

LIENCHBZNNMNKG-OJFNHCPVSA-N

InChI=1S/C23H32F3N5O4/c1-21(2,3)16(30-20(35)23(24,25)26)19(34)31-10-13-14(22(13,4)5)15(31)18(33)29-12(9-27)8-11-6-7-28-17(11)32/h11-16H,6-8,10H2,1-5H3,(H,28,32)(H,29,33)(H,30,35)/t11-,12-,13-,14-,15-,16+/m0/s1

(1R,2S,5S)-N-((S)-1-cyano-2-((S)-2-oxopyrrolidin-3-yl)ethyl)-3-((S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide

Nirmatrelvir; PF-07321332; PF 07321332; P7R9A5P7H32; Nirmatrelvir; Paxlovid; PF-07321332; PF07321332; Nirmatrelvir [USAN]; UNII-7R9A5P7H32; F07321332; brand name Paxlovid;

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)

DMSO : 100~140 mg/mL ( 200.18~280.26 mM )
Ethanol : 50 ~100 mg/mL

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+90% Corn Oil: ≥ 2.08 mg/mL (4.16 mM)

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