Celgosivir  (Synonyms: MBI 3253; MDL 28574; MX3253)

Celgosivir (MBI 3253; MDL 28574; MX3253) is an α-glucosidase I inhibitor; inhibits bovine viral diarrhoea virus (BVDV) with an IC₅₀ of 1.27 μM in in vitro assay.

Celgosivir is more effective (IC₅₀=20 μM) than the parent molecule (IC₅₀=254 μM) at causing the accumulation of glucosylated oligosaccharides in HIV-infected cells by inhibition of glycoprotein processing. Celgosivir exhibits potent antiviral activity against HIV-1 with an IC₅₀ of 2.0±2.3 μM^[1]. Bovine viral diarrhoea virus (BVDV) is a closely related virus of hepatitis C virus (HCV). Celgosivir inhibits BVDV with IC₅₀ values of 16 and 47 μM in plaque assay and cytopathic effect assay, respectively^[2]. Celgosivir inhibits DENV2 replication with an EC₅₀ of 0.2 μM. The EC₅₀ values against DENV1, 3 and 4 are less than 0.7 μM^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Celgosivir fully protects AG129 mice from lethal infection with a mouse adapted dengue virus at a dose of 50 mg/kg twice daily (BID) for 5 days and is effective even after 48 h delayed treatment. The protection by celgosivir is dose- and schedule-dependent and that a twice-a-day regimen of 50, 25 or 10 mg/kg is more protective than a single daily dose of 100 mg/kg. Pharmacokinetics studies of celgosivir in mice shows that it rapidly metabolizes to castanospermine^[4]. During primary infection with a mouse-adapted DENV strain S221, mice shows increased viremia on day 3, yet 80% survived day 10 with virus completely cleared by day 8^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

259.30

C₁₂H₂₁NO₅

121104-96-9

Solid

O[C@@H]1[C@]2([H])[C@@H](O)[C@H](O)[C@@H](OC(CCC)=O)CN2CC1

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

• [1]. Taylor DL, et al. Inhibition of alpha-glucosidase I of the glycoprotein-processing enzymes by 6-O-butanoylcastanospermine (MDL 28,574) and its consequences in human immunodeficiency virus-infected T cells. Antimicrob Agents Chemother. 1994 Aug;38(8):1780-7.  [Content Brief]

  [2]. Rathore AP, et al. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes andprotects against lethal challenge mouse model. Antiviral Res. 2011 Dec;92(3):453-60.  [Content Brief]

  [3]. Whitby K, et al. Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV: implications for the treatment of hepatitis C. Antivir Chem Chemother. 2004 May;15(3):141-51.  [Content Brief]

  [4]. Watanabe S, et al. Dose- and schedule-dependent protective efficacy of celgosivir in a lethal mouse model for dengue virus infection informs dosing regimen for a proof of concept clinical trial. Antiviral Res. 2012 Oct;96(1):32-5.  [Content Brief]