Umifenovir has been shown to possess strong and extensive antiviral properties against a wide range of viruses, such as the influenza A, B, and C viruses; respiratory syncytial virus; SARS-CoV; adenovirus; parainfluenza type 5; rhinovirus 14; coxsackievirus B5; hantavirus; chikungunya virus; hepatitis B virus; and hepatitis C virus [1].

Mice with influenza who are given umifenovir orally at doses of 25 and 45 mg/ml have been shown to survive [3].

Animal/Disease Models: balb/c (Bagg ALBino) mouse (6-8 weeks old), mice were inoculated intranasally (in) with 2 times 50% mouse lethal dose (MLD50) of A/Guangdong/GIRD07/09 (H1N1) (104.5TCID50/ mL)), the volume is 20mL[3].
Doses: 1.25 mg/mL (25 mg/kg/day) and 2.25 mg/mL (45 mg/kg/day) one day before infection and 3 days after infection (dpi), total volume 500mL. Oral administration
Experimental Results: Compared with the virus group, 45mg/mL can improve the survival rate and inhibit weight loss, and 25mg/mL and 45mg/mL can inhibit the increase in the lung index of mice.

Absorption, Distribution and Excretion
Umifenvir is rapidly absorbed after oral administration, with an estimated time to peak concentration (Tmax) of 0.65–1.8 hours. Peak plasma concentration (Cmax) is estimated to be 415–467 ng/mL and appears to increase linearly with dose. The estimated AUC0-inf after oral administration is approximately 2200 ng/mL/h. The primary route of excretion is feces. Approximately 40% of the ingested dose is excreted unchanged, with 38.9% excreted via bile and 0.12% via the kidneys. The total recovery of the unchanged drug and its metabolites in urine is less than 1% of the ingested dose. Data on the volume of distribution of umifenvironment are currently unavailable. In a study of healthy Chinese male volunteers, the oral clearance of umifenvironment was found to be 99 ± 34 L/h.

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Metabolism/Metabolites
Umifenvir is extensively metabolized in the body, primarily in the liver and intestinal microsomes. Approximately 33 metabolites have been observed in human plasma, urine, and feces. The main phase I metabolic pathways include sulfoxide formation, N-demethylation, and hydroxylation, followed by phase II sulfate and glucuronide conjugation. In urine, the main metabolites are sulfate and glucuronide conjugates, while in feces, the main substances are unmetabolized parent drug (approximately 40%) and M10 metabolites (approximately 3.0%). In plasma, the main metabolites are M6-1, M5, and M8—of which M6-1 appears to be the most important due to its high plasma exposure and long elimination half-life (~25 hours), making it a potentially important factor in the safety and efficacy of umifenvironment. Enzymes involved in the metabolism of umifenvironmentally active drugs include members of the cytochrome P450 family (primarily CYP3A4), flavin-containing monooxygenases (FMOs), and members of the UDP-glucuronyltransferase (UGT) family (especially UGT1A9 and UGT2B7). Known metabolites of arbidol include (2S,3S,4S,5R)-6-[6-bromo-4-[(dimethylamino)methyl]-3-ethoxycarbonyl-1-methyl-2-(phenylthiomethyl)indol-5-yl]oxy-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid. The estimated half-life of orally administered umifenvironmentally active drugs is 17–21 hours. The serum half-lives of the M5, M6-1, and M8 metabolites are 26.3 ± 5.9, 25.0 ± 5.4, and 25.7 ± 8.8, respectively.

Protein Binding
There is currently no data on protein binding of umifenvironment.

[1]. Arbidol as a broad-spectrum antiviral: an update. Antiviral Res. 2014 Jul;107:84-94. doi: 10.1016/j.antiviral.2014.04.006. Epub 2014 Apr 24.

[2]. Antiviral Activity of Umifenovir In Vitro against a Broad Spectrum of Coronaviruses, Including the Novel SARS-CoV-2 Virus. Viruses. 2021 Aug 23;13(8):1665.

[3]. Inhibition of the infectivity and inflammatory response of influenza virus by Arbidol hydrochloride in vitro and in vivo (mice and ferret). Biomed Pharmacother. 2017 Jul;91:393-401.

Pharmacodynamics
Umifenvir exerts its antiviral effects through direct virucidal activity and by inhibiting one or more stages of the viral life cycle. Its broad-spectrum activity covers both enveloped and non-enveloped RNA and DNA viruses. Umifenvir is well-tolerated and has a broad therapeutic window—in experimental animals, even doses 100 times higher than human doses did not induce any pathological changes. Umifenvir does not appear to lead to significant viral resistance. Cases of umifenvir-resistant influenza viruses have been identified, showing a single mutation in the influenza hemagglutinin HA2 subunit, suggesting that resistance arises by inhibiting umifenvir's membrane fusion-related activity. The mechanisms by which other viruses develop umifenvironment require further investigation.

C22H25BRN2O3S

477.4

476.076

131707-25-0

Umifenovir hydrochloride;131707-23-8

131411

Off-white to light yellow solid powder

1.4±0.1 g/cm3

591.8±50.0 °C at 760 mmHg

311.7±30.1 °C

0.0±1.7 mmHg at 25°C

1.620

4.64

1

5

8

29

546

0

KCFYEAOKVJSACF-UHFFFAOYSA-N

InChI=1S/C22H25BrN2O3S/c1-5-28-22(27)20-18(13-29-14-9-7-6-8-10-14)25(4)17-11-16(23)21(26)15(19(17)20)12-24(2)3/h6-11,26H,5,12-13H2,1-4H3

ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-(phenylsulfanylmethyl)indole-3-carboxylate

Arbidol; umifenovir;

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 (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~50 mg/mL (~104.73 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.)