[CAS NO. 141117-12-6] Celgosivirhydrochloride
PRODUCTS SPECIFICATIONS [141117-12-6]
DESCRIPTION [141117-12-6]
Overview
| MDL | MFCD30738181 |
|---|---|
| Molecular Weight | 295.76 |
| Molecular Formula | C12H22ClNO5 |
| SMILES | O[C@@H]1[C@]2([H])[C@@H](O)[C@H](O)[C@@H](OC(CCC)=O)CN2CC1.Cl[H] |
Summary
Celgosivir hydrochloride (MBI 3253 hydrochloride; MDL 28574 hydrochloride; MX3253 hydrochloride) is an α-glucosidase I inhibitor; inhibits bovine viral diarrhoea virus (BVDV) with an IC 50 of 1.27 μM in in vitro assay.
IC50 & Target
IC50: 1.27 μM (α-glucosidase I) [1]
In Vitro
Celgosivir is more effective (IC 50 =20 μM) than the parent molecule (IC 50 =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 IC 50 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 IC 50 values of 16 and 47 μM in plaque assay and cytopathic effect assay, respectively [2] . Celgosivir inhibits DENV2 replication with an EC 50 of 0.2 μM. The EC 50 values against DENV1, 3 and 4 are less than 0.7 μM [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00002150 | Hoechst Marion Roussel|NIH AIDS Clinical Trials Information Service |
HIV Infections
|
Phase 2 | |
| NCT01619969 | Singapore General Hospital|Duke-NUS Graduate Medical School |
Dengue Fever
|
July 2012 | Phase 1|Phase 2 |
| NCT00157534 | BioWest Therapeutics Inc |
Hepatitis C, Chronic
|
October 2004 | Phase 2 |
| NCT00292084 | BioWest Therapeutics Inc |
Hepatitis C, Chronic
|
February 2006 | Phase 2 |
| NCT02569827 | Singapore General Hospital|Duke-NUS Graduate Medical School|60 Degrees Pharmaceuticals LLC |
Dengue Fever
|
December 2018 | Phase 1|Phase 2 |
| NCT00332176 | BioWest Therapeutics Inc |
Chronic Hepatitis C
|
June 2006 | Phase 2 |
| NCT00217139 | BioWest Therapeutics Inc |
Hepatitis C, Chronic
|
September 2005 | Phase 2 |
| NCT00002329 | Hoechst Marion Roussel|NIH AIDS Clinical Trials Information Service |
HIV Infections
|
Phase 1 | |
| NCT00002151 | Hoechst Marion Roussel|NIH AIDS Clinical Trials Information Service |
HIV Infections
|
Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
H 2 O : ≥ 100 mg/mL ( 338.11 mM )
DMSO : 100 mg/mL ( 338.11 mM ; Need ultrasonic)
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.3811 mL | 16.9056 mL | 33.8112 mL |
| 5 mM | 0.6762 mL | 3.3811 mL | 6.7622 mL |
| 10 mM | 0.3381 mL | 1.6906 mL | 3.3811 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 100 mg/mL (338.11 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (8.45 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (8.45 mM); Clear solution
References
- [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-
- [2] 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.
- [3] 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.
- [4] 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.