cAIM(PS)2 Difluor (Rp/Sp)
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cAIMP bisphosphorothioate and difluorinated, a STING ligand
cAIM(PS)2 Difluor (Rp/Sp) is composed of Rp/Sp-isomers of the bisphosphorothioate derivative of cAIMP, an analog of the bacterial cyclic dinucleotide (CDN) 3'3'-cGAMP . cAIMP and cAIM(PS)2 Difluor (Rp/Sp) are novel STING (stimulator of interferon genes)-activating synthetic CDNs. Unlike natural CDNs, whose constituent nucleosides are guanosine and/or adenine, cAIMP and its derivatives contain one adenine nucleoside and one inosine nucleoside. cAIM(PS)2 Difluor (Rp/Sp) is composed of two 2’-deoxynucleosides with a fluorine atom at 2’ position of each nucleoside.
As STING agonists are being studied for their potential in immunotherapy and vaccination, an obstacle to their therapeutic utility is their lability to enzymatic hydrolysis by various nucleases and phosphodiesterases. The replacement of phosphodiester linkages with phosphorothioate linkages is a well-known strategy for improving resistance to enzymatic cleavage . Moreover, fluorine atoms were incorporated into this analog as a means to improve its stability . Indeed when compared to STING agonists such as 2’3’‑cGAMP, this analog (referred to as compound 53 by Lioux et al. ) is not only more resistant to enzymatic cleavage but also more potent .
STING ligands such as cAIM(PS)2 Difluor (Rp/Sp) induce production of type I interferons (IFNs) through IRFs and of proinflammatory cytokines through the NF-κB pathway. To facilitate their study, InvivoGen has developed stable reporter cells in two well established immune cell models: THP-1 human monocytes and RAW 264.7 murine macrophages. These cells express inducible SEAP and/or Lucia luciferase reporter genes under the control of an IRF-inducible or NF-κB-inducible promoter.
1. Lioux T. et al., 2016. Design, synthesis, and biological evaluation of novel cyclic adenosineinosine monophosphate (cAIMP) analogs that activate stimulator of interferon genes (STING). J Med Chem. 59:10253-10267.
2. Yan H. et al., 2008. Synthesis and immunostimulatory properties of the phosphorothioate analogues of cdiGMP. Bioorg. Med. Chem. Lett. 18, 5631–5634.
3. Böhm HJ. et al., 2004. Fluorine in medicinal chemistry. Chembiochem. 5:637-43.
THP1-Dual™ cells were stimulated for 24 hours with human IFN-β (1 x 104 U/ml), TNF-α (300 pg/ml), cAIMP, cAIMP Difluor, cAIM(PS)2 Difluor (Rp/Sp), 2’3’-cGAMP and 2’3’-cGAM(PS)2 (Rp/Sp). All CDNs were used at 10 μg/ml.
IRF induction was determined by measuring the relative light units (RLUs) in a luminometer using QUANTI‑Luc™, a Lucia luciferase detection reagent. The IRF induction of each ligand is expressed relative to that of hIFN-β at 1 x 104 U/ml (taken as 100%).
THP1-Dual™ cells were stimulated for 24 hours with human IFN-β (1 x 104 U/ml), TNF-α (300 pg/ml), cAIMP, cAIMP Difluor, cAIM(PS)2 Difluor (Rp/Sp), 2’3’-cGAMP and 2’3’-cGAM(PS)2 (Rp/Sp). All CDNs were used at 10 μg/ml.
NF-κB induction was determined using QUANTI‑Blue™, a SEAP detection reagent, and by reading the optical density (OD) at 655 nm. TNF-α has been included as a positive control to activate the NF-κB signaling pathway.
Synonym: (Rp/Sp) c-[2’FdAM(PS)-2’FdIM(PS]) sodium salt
Formula: C20H21F2N9O9P2S2 .2Na
Molecular weight: 695.5 (free acid), 739.5 (sodium salt)
Solubility: 50 mg/ml in water
- Purity and structure has been determined by LC/MS and NMR: ≥ 95%
- The biological activity has been confirmed using cellular assays.
- The absence of bacterial contamination (e.g. lipoproteins & endotoxins) has been confirmed using HEK-Blue™ TLR4 and HEK-Blue™ TLR2 cells.
- 100 μg of cAIM(PS)2 Difluor (Rp/Sp) provided lyophilized.
Note: This product is sterile filtered prior to lyophilization.
cAIM(PS)2 Difluor (Rp/Sp) is a mixture of Rp/Sp diastereoisomers.
- 1.5 ml endotoxin-free water
cAIM(PS)2 Difluor (Rp/Sp) chemical structureBack to the top