cAIMP (CL592)

Cyclic (adenine monophosphate- inosine monophosphate)

InvivoGen's cAIMP (also known as CL592) is a novel STING (stimulator of interferon genes)-activating synthetic cyclic dinucleotide (CDN) [1].

It is an analog of the bacterial CDN 3’3’-cGAMP. Unlike natural CDNs, whose constituent nucleosides are guanosine and/or adenine, cAIMP contains one adenine nucleoside and one inosine 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. 

Interestingly, when compared to the reference agonists for human (2’3’‑cGAMP) and murine (DMXAA) STING, cAIMP (referred to as compound 9 by Lioux et al. [1]) exhibits potency similar to 2’3’-cGAMP and is more potent than DMXAA in inducing interferon regulatory factor (IRF) and NF-κB pathways in a STING‑dependent manner [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.

Reference:

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.

Figures

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 (1x10⁴U/ml), TNF-α (300pg/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 10μg/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.

Specifications

Source: Synthetic

Synonym: 3’3’-cAIMP sodium salt, 3’3’-c(ApIp) sodium salt

CAS: 1507367-51-2

Formula: C₂₀H₂₃N₉O₁₃P₂ .2Na

Molecular weight: 659.4 (free acid), 703.4 (sodium salt)

Solubility: 50 mg/ml in water

Quality control:

• Purity and structure has been determined by LC/MS and NMR: ≥ 95%
• The biological activity of cAIMP 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.

Contents

• 500 μg of cAIMP provided lyophilized.
  Note: cAIMP is sterile filtered prior to lyophilization.
• 1.5 ml endotoxin-free water

Description

cAIMP chemical structure