cAIMP Difluor (CL614) - STING Agonist

cAIMP difluorinated

InvivoGen's cAIMP Difluor (also known as CL614) is a derivative of cAIMP, an analog of the bacterial cyclic dinucleotide (CDN) 3’3’-cGAMP [1].

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.

STING ligands such as cAIMP induce the production of type I interferons (IFNs) and of proinflammatory cytokines through the IRF and NF-κB pathways, respectively.

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 [2]. 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.  [1]) 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 [1]. Interestingly, cAIMP Difluor is more resistant than 2’3’‑cGAMP and cAIMP to cleavage by certain nuclease and phosphodiesterase enzymes [1].

To facilitate the srudy of STING ligands, 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 and NF-κB promoter. 

References:

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