cAIM(PS)2 Difluor (Rp/Sp) (CL656) - STING Agonist

cAIMP bisphosphorothioate and difluorinated

ABOUT

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 [1]. 
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 [5]. CL656 can be considered a clinically relevant safe STING agonist since it has been successfully administered in humans in combination with exosomes (ExoSTING) [3,5].  

Key Features

  • 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 [5]. 
     
  • A clinically relevant safe STING agonist successfully administered in humans to treat advanced solid tumors [3,5].
     
  • 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 [6].
     
  • 2’3’‑cGAMP, cAIM(PS)2 Difluor (Rp/Sp) (referred to as compound 53 by Lioux et al. [1]) is more potent than 2’3’‑cGAMP for STING activation [1].

 

CL-656 was licensed by Kayla Therapeutics to Codiak Biosciences for therapeutic purposes.
 

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.

 

 

References:

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.
5. https://clinicaltrials.gov/ct2/show/NCT04592484
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.

All products are for internal research use only, and not for human or veterinary use.

SPECIFICATIONS

Specifications

Source
Synthetic
Target

STING

CAS number
1951464-79-1
Chemical formula

C20H21F2N9O9P2S2 •2Na

Molecular weight
739.5 g/mol
Purity
≥ 95% (LC/MS and NMR)
Solubility

50 mg/ml in water

Appearance (form)
Lyophilized pellet
Appearance (color)
White
Tested applications

Cellular assays

Quality control

Each lot is functionally tested and validated.

CONTENTS

Contents

  • Product: 
    cAIM(PS)2 Difluor (Rp/Sp)
  • Cat code: 
    tlrl-nacairs-05
  • Quantity: 
    5 x 100 μg
Includes:

1.5 ml endotoxin-free water

Shipping & Storage

  • Shipping method:  Room temperature
  • Storage:

    • -20°C

    Caution:

    • Avoid repeated freeze-thaw cycles

DOCUMENTS

Documents

cAIM(PS)2 Difluor (Rp/Sp)

Technical Data Sheet

Validation Data Sheet

Safety Data Sheet

Certificate of analysis

Need a CoA ?

CUSTOMER SERVICE & TECHNICAL SUPPORT

Question about this product ?