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Chemical Structure| 58944-73-3 Chemical Structure| 58944-73-3

Structure of Sinefungin
CAS No.: 58944-73-3

Chemical Structure| 58944-73-3

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Sinefungin is an inhibitor of Zika virus methyltransferase.

Synonyms: Antibiotic 32232RP; A-9145; RP 32232

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Product Citations

Product Citations

Zhou, Jujun ; Deng, Youchao ; Iyamu, Iredia D. ; Horton, John R. ; Yu, Dan ; Hajian, Taraneh , et al.

Abstract: S-Adenosyl-L-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-Et moiety at the sulfur atom off the ribose ring. Compound 11a (IC50 = 0.15 μM) is 10x and 5x more potent against CamA than 6e and 7, resp. The structure of the CamA-DNA-inhibitor complex revealed that 11a adopts a U-shaped conformation, with the two branches folded toward each other, and the aliphatic and aromatic rings at the two ends interacting with one another. 11a occupies the entire hydrophobic surface (apparently unique to CamA) next to the adenosine binding site. Our work presents a hybrid knowledge-based and fragment-based approach to generating CamA inhibitors that would be chem. agents to examine the mechanism(s) of action and therapeutic potentials of CamA in C. difficile infection.

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Product Details of Sinefungin

CAS No. :58944-73-3
Formula : C15H23N7O5
M.W : 381.39
SMILES Code : O=C(O)[C@@H](N)CC[C@H](N)C[C@H]1O[C@@H](N2C=NC3=C(N)N=CN=C23)[C@H](O)[C@@H]1O
Synonyms :
Antibiotic 32232RP; A-9145; RP 32232
MDL No. :MFCD00865623

Safety of Sinefungin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Related Pathways of Sinefungin

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Vero cells 2.56 mM 20 hours To evaluate the effect of SIN on replication of vesicular stomatitis virus(VSV), results showed that SIN significantly inhibited viral replication. J Virol. 2007 Apr;81(8):4104-15
Saccharomyces cerevisiae 10 µM 24 hours To study the inhibitory effect of Sinefungin on yeast growth, it was found that Sinefungin inhibits yeast growth by inhibiting the function of the AdoMet transporter Sam3. Nucleic Acids Res. 2007;35(20):6895-903
BHK cells 2.56 mM 24 hours To evaluate the effect of SIN on replication of vesicular stomatitis virus(VSV), results showed that SIN significantly inhibited viral replication. J Virol. 2007 Apr;81(8):4104-15

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague-Dawley rats Immunosuppressed rat model Oral 0.01 to 10.0 mg/kg/day Administered from day 7 to day 21 Sinefungin demonstrated curative and preventive activity against C. parvum infection in the immunosuppressed rat model, with dose-related suppression of oocyst shedding correlated with oocyst disappearance from ileal sections. Antimicrob Agents Chemother. 1993 Apr;37(4):889-92

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.62mL

0.52mL

0.26mL

13.11mL

2.62mL

1.31mL

26.22mL

5.24mL

2.62mL

References

 

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