cAIM(PS)2 Difluor (Rp/Sp) (CL656)
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cAIMP bisphosphorothioate and difluorinated, a STING ligand
2 x 100 µg
cAIMP bisphosphorothioate and difluorinated
InvivoGen's cAIM(PS)2 Difluor (Rp/Sp) (also known as CL656) is a synthetic cyclic dinucleotide (CDN) and potent agonist of the endoplasmic reticulum-resident receptor STING (stimulator of interferon genes) [1-3]. It is composed of Rp/Sp-isomers of the bisphosphorothioate derivative of cAIMP, an analog of the bacterial cyclic dinucleotide (CDN) 3'3'-cGAMP [1-2]. The binding of cAIM(PS)2 Difluor (Rp/Sp) to STING triggers the expression of interferon-β (IFN-β) and nuclear factor-κB (NF-κB) dependent inflammatory cytokines .
STING has been a privileged target for developing immunomodulatory therapeutics [3, 4]. Of note, cAIM(PS)2 Difluor (Rp/Sp) has entered clinical trials for treating advanced/metastatic, recurrent, solid tumors, with emphasis on squamous cell carcinoma of the head and neck, triple-negative breast cancer, anaplastic thyroid carcinoma, and cutaneous squamous cell carcinoma .
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 the 2’ position of each nucleoside for improved stability .
In addition, this cAIMP analog contains two phosphorothioate diester linkages, which prevent its degradation by the phosphodiesterases that are present in host cells or in the systemic circulation .
- 2’3’‑cGAMP, cAIM(PS)2 Difluor (Rp/Sp) (referred to as compound 53 by Lioux et al. ) is more potent than 2’3’‑cGAMP for STING activation .
Note: InvivoGen has developed stable STING 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. Cyclic dinucleotides for cytokine induction, patent US10011630B2 and foreign equivalents.
3. Jang S., et al. 2021. ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance. Commun. Biol. 4:497.
4. Zhang H., et al. 2020. Targeting Stimulator of Interferon Genes (STING): a medicinal chemistry perspective. Journal of Medicinal Chemistry. 63(8):3785.
6. Böhm H.J. et al., 2004. Fluorine in medicinal chemistry. Chembiochem. 5:637-43.
7. Yan H. et al., 2008. Synthesis and immunostimulatory properties of the phosphorothioate analogs of cdiGMP. Bioorg. Med. Chem. Lett. 18, 5631–5634.
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.
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.
2x 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