WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H529538
CAS#: 121104-96-9 (free base)
Description: Celgosivir (free base) is an α-glucosidase inhibitor potentially for the treatment of dengue fever.
Hodoodo Cat#: H529538
Name: Celgosivir free base
CAS#: 121104-96-9 (free base)
Chemical Formula: C12H21NO5
Exact Mass: 259.14
Molecular Weight: 259.300
Elemental Analysis: C, 55.58; H, 8.16; N, 5.40; O, 30.85
Related CAS #: 121104-96-9 (free base) 141117-12-6 (HCl),
Synonym: Celgosivir (free base); 60-P-001; MBI-3253; MDL-28574; MX-3253; VIR-222; 60P001; MBI3253; MDL28574; MX3253; VIR222; 60 P 001; MBI 3253; MDL 28574; MX 3253; VIR 222
IUPAC/Chemical Name: (1R,6R,7R,8S,8aS)-1,7,8-trihydroxyoctahydroindolizin-6-yl butyrate
InChi Key: HTJGLYIJVSDQAE-PPJKGSGRSA-N
InChi Code: InChI=1S/C12H21NO5/c1-2-3-9(15)18-8-6-13-5-4-7(14)10(13)12(17)11(8)16/h7-8,10-12,14,16-17H,2-6H2,1H3/t7-,8-,10+,11+,12+/m1/s1
SMILES Code: CCCC(O[C@@H]1CN2CC[C@@H](O)[C@@]2([H])[C@H](O)[C@H]1O)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | 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. |
| In vitro activity: | To examine the antiviral effect of celgosivir in vitro, the cell-based flavivirus immune detection (CFI) assay, which comprises the complete replication cycle of DENV, was used. BHK-21 cells were infected with a clinical isolate of DENV2 at an MOI of 0.3 in the presence of different concentrations of celgosivir, and virus E protein was quantified 48 h later using 4G2 antibody. The result showed an inhibitory effect of celgosivir on DENV2 replication with a half maximal effective concentration (EC50) value of ∼0.2 μM (Fig. 1A). Similarly, EC50 values against DENV1, 3 and 4 were obtained (Table 1) and found to be below 0.7 μM. Furthermore, immunofluorescence microscopy confirmed the effect of celgosivir on DENV2, since NS1 was hardly detected in the drug-treated cells (Fig. 1B). Interestingly, celgosivir is about 100 times more effective against DENV2 than the parent compound castanospermine (Fig. S1). These results suggest that celgosivir has a robust inhibitory effect against all four DENV serotypes (DENV1-4). Reference: Antiviral Res. 2011 Dec;92(3):453-60. https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(11)00452-9 |
| In vivo activity: | Previously it was shown that celgosivir significantly reduced viremia in AG129 mice infected with a clinical strain of DENV2 (TSV01). The recently developed lethal DENV infection model was used to test the efficacy of celgosivir. During primary infection with a mouse-adapted DENV strain S221, mice showed increased viremia on day 3, yet 80% survived day 10 (Fig. 4A and B) with virus completely cleared by day 8 (data not shown). On the other hand, mice infected with the same virus dose 24 h after passive immunization with 4G2 antibody (ADE infection model) displayed very high viremia on day 3 (Fig. 4B), with severe morbidity and 100% mortality by day 5 (Fig. 4A). To test the antiviral effect of celgosivir in both primary and severe ADE infection models, mice were treated with 50 mg/kg of celgosivir, twice-a-day, for 5 days starting from the day of infection. For delayed treatment studies, the twice a day dose celgosivir treatment was administered 1 or 2 days post-infections. Remarkably, mice treated from the day of infection showed 100% survival and those treated from day 1 or day 2-post-infection showed 75% and 50% survival, respectively (Fig. 4A). Viremia data corresponding to the survival curve showed significant reduction in the viral burden of celgosivir-treated groups (Fig. 4B). The immune fitness of the surviving mice was also determined by kinetic serum cytokine analysis. In all cases virally challenged mice developed a strong Th1 polarized signature by day 3, which in the case of virus treatment alone progressed into a systemic inflammatory signature by day 7. Interestingly, these data show that celgosivir-treated mice were capable of maintaining significantly higher levels of cytokines such as IFN-γ, IL-9, RANTES, which are associated with immune clearance of viral pathogens and lower levels of proinflammatory cytokines including TNF-α, MCP-1 and IL-6, which are associated with lethal immune pathology during DENV infection (Fig. 4C). Cumulatively, these data suggest that celgosivir is a robust antiviral compound, effective in an in vivo model of both primary and severe ADE DENV infection. Reference: Antiviral Res. 2011 Dec;92(3):453-60. https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(11)00452-9 |
The following data is based on the product molecular weight 259.30 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Rathore AP, Paradkar PN, Watanabe S, Tan KH, Sung C, Connolly JE, Low J, Ooi EE, Vasudevan SG. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res. 2011 Dec;92(3):453-60. doi: 10.1016/j.antiviral.2011.10.002. Epub 2011 Oct 12. PMID: 22020302. |
| In vivo protocol: | 1. Rathore AP, Paradkar PN, Watanabe S, Tan KH, Sung C, Connolly JE, Low J, Ooi EE, Vasudevan SG. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res. 2011 Dec;92(3):453-60. doi: 10.1016/j.antiviral.2011.10.002. Epub 2011 Oct 12. PMID: 22020302. 2. Watanabe S, Rathore AP, Sung C, Lu F, Khoo YM, Connolly J, Low J, Ooi EE, Lee HS, Vasudevan SG. 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. doi: 10.1016/j.antiviral.2012.07.008. Epub 2012 Jul 31. PMID: 22867971. |
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2: Watanabe S, Rathore AP, Sung C, Lu F, Khoo YM, Connolly J, Low J, Ooi EE, Lee HS, Vasudevan SG. 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. doi: 10.1016/j.antiviral.2012.07.008. PubMed PMID: 22867971.
3: Sung C, Wei Y, Watanabe S, Lee HS, Khoo YM, Fan L, Rathore AP, Chan KW, Choy MM, Kamaraj US, Sessions OM, Aw P, de Sessions PF, Lee B, Connolly JE, Hibberd ML, Vijaykrishna D, Wijaya L, Ooi EE, Low JG, Vasudevan SG. Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients. PLoS Negl Trop Dis. 2016 Aug 10;10(8):e0004851. doi: 10.1371/journal.pntd.0004851. PubMed PMID: 27509020; PubMed Central PMCID: PMC4980036.
4: Rathore AP, Paradkar PN, Watanabe S, Tan KH, Sung C, Connolly JE, Low J, Ooi EE, Vasudevan SG. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res. 2011 Dec;92(3):453-60. doi: 10.1016/j.antiviral.2011.10.002. PubMed PMID: 22020302.
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