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cAIMP difluorinated, a STING ligand
cAIMP Difluor is a derivative of cAIMP, an analog of the bacterial cyclic dinucleotide (CDN) 3’3’-cGAMP . cAIMP and cAIMP Difluor 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. cAIMP Difluor is composed of two 2’-deoxynucleosides with a fluorine atom at 2’ position of each nucleoside.
The incorporation of fluorine into biologically active molecules is commonly used in medicinal chemistry to improve their metabolic stability or to modulate physicochemical properties such as lipophilicity . Moreover, the introduction of a fluorine atom can change the biological activities of a molecule. Indeed cAIMP Difluor (referred to as compound 52 by Lioux et al. ) more potently induces interferon regulatory factor (IRF) and NF-κB pathways in a STING‑dependent manner when compared to STING agonists such as 2’3’‑cGAMP and DMXAA . Interestingly, cAIMP Difluor is more resistant than 2’3’‑cGAMP and cAIMP to cleavage by certain nuclease and phosphodiesterase enzymes .
STING ligands such as cAIMP Difluor 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 adenosine-inosine monophosphate (cAIMP) analogs that activate stimulator of interferon genes (STING). J Med Chem. 59(22):10253-10267.
2. Böhm HJ. et al., 2004. Fluorine in medicinal chemistry. Chembiochem. 5(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: c-(2’FdAMP-2’FdIMP) sodium salt
Formula: C20H21F2N9O11P2 .2Na
Molecular weight: 663.4 (free acid), 707.4 (sodium salt)
Solubility: 50 mg/ml in water
- Purity and structure has been determined by LC/MS and NMR: ≥ 95%
- The biological activity of cAIMP Difluor 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.
- 250 μg of cAIMP Difluor provided lyophilized.
Note: cAIMP Difluor is sterile filtered prior to lyophilization.
- 1.5 ml endotoxin-free water
cAIMP Difluor chemical structureBack to the top