CL845 (cAIM(PS) Difluor (Rp)) - VacciGrade™ - STING Agonist

(Rp) cyclic (2'FdAM(PS)-2'FdIMP) | Th1/Th2 response

ABOUT

cAIMP monophosphorothioate and difluorinated - Th1/Th2 response adjuvant

cAIM(PS) Difluor (Rp) (also known as CL845) is a proprietary* synthetic cyclic dinucleotide (CDN) and potent agonist of STING (stimulator of interferon genes), an endoplasmic reticulum-resident PRR (pattern recognition receptor). This AIMP monophosphorothioate and difluorinated CDN is an analog of the clinical STING agonists CL656 (cAIM(PS)2 Difluor (Rp/Sp)) and ADU-S100/MIW815.

AIMP and its derivatives have been engineered for enhanced stability and resistance to enzymatic cleavage to support clinical translation of STING agonists. CL845 is used as a building block to generate conjugatable STING agonists, including STG-982, STG-968, and STG-1151, for the development of antibody–drug conjugates (ADCs, ISACs) and antigen–adjuvant conjugates (AACs).

More details
 

The binding of CL845 to STING triggers downstream IRF (interferon regulatory factor) and NF-κB (nuclear factor-κB) signaling pathways. As expected, the structural features of CL845 enhance its STING activation potency relative to natural 2'3'-cGAMP CDN (see figures).
 

Key Features:

  • Potent activator of human and mouse STING
  • Analog of the clinically-relevant CL656 and ADU-S100/MIW815
  • VacciGrade™: a high-quality pre-clinical grade

Applications:

  • Induction of STING-dependent cellular responses
  • Adjuvantation studies

 

*CL845 is a cyclic dinucleotide STING agonist scaffold belonging to a family of fluorinated and phosphorothioate-modified CDNs described in InvivoGen-origin patent US10011630B2. 

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

Chemical structure of CL845
Chemical structure of CL845

VacciGrade™

VacciGrade™ is a high-quality pre-clinical grade, suitable for in vivo studies. VacciGrade™ products are filter-sterilized (0.2 µm) and filled under strict aseptic conditions in a clean room. The absence of  bacterial contamination is assessed by a sterility test using a pharmacopeia-derived assay.

SPECIFICATIONS

Specifications

Source
Synthetic
Synonyms
(Rp) c-(2'FdAM(PS)-2'FdIMP)
CL845
Target

STING

CAS number
2413989-01-0
Chemical formula

C20H21F2N9O10P2S •2Na

Molecular weight
679.45 g/mol (acid form) / 723.41 g/mol (sodium salt)
Working concentration

1-100 µg/ml

Purity
≥ 95% (LC/MS and NMR)
Solubility

50 mg/ml in water

Appearance (form)
Lyophilized
Reconstitution buffer
Endotoxin-free water (provided)
Sterility

Sterility guaranteed

Endotoxin

The absence of bacterial contamination (e.g. lipoproteins and endotoxins) is confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Tested applications

STING bioassays

Quality control

Each lot is functionally tested and validated. 

CONTENTS

Contents

  • Product: 
    cAIM(PS) Difluor (Rp) (CL845) VacciGrade™
  • Cat code: 
    vac-nacaifr
  • Quantity: 
    250 µg
Includes:

1.5 ml endotoxin-free water

Shipping & Storage

  • Shipping method:  Room temperature

    • Storage:

    • -20°C
    Stability: -20°C for up to 6 months

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

cAIM(PS) Difluor (Rp) (also referred to as CL845) is a proprietary* potent synthetic STING (stimulator of interferon genes) agonist derived from cAIMP, an analog of the bacterial cyclic dinucleotide (CDN) 3'3'-cGAMP [1].

STING agonists induce the production of type I interferons and proinflammatory cytokines through the IRF (interferon regulatory factor) and NF-κB pathways, respectively. Due to their potent immunostimulatory properties, CDNs are widely investigated as vaccine adjuvants and immunotherapy agents. However, the clinical translation of natural CDNs has been limited by their susceptibility to enzymatic degradation by nucleases and phosphodiesterases. To address this limitation, cAIMP and its derivatives have been engineered for enhanced stability and resistance to enzymatic cleavage [2,3]. cAIM(PS) Difluor (Rp) incorporates one phosphorothioate linkage and a fluorine atom at the 2' position of each nucleoside [4,5]. 

cAIM(PS) Difluor (Rp) is used as a building block to generate conjugatable STING agonists, including STG-982, STG-968, and STG-1151, for the development of antibody–drug conjugates (ADCs, ISACs) and antigen–adjuvant conjugates (AACs).
 

*CL845 is a cyclic dinucleotide STING agonist scaffold belonging to a family of fluorinated and phosphorothioate-modified CDNs described in InvivoGen-origin patent US10011630B2. 

 

References:

1. Zhang H., et al. 2020. Targeting Stimulator of Interferon Genes (STING): a medicinal chemistry perspective. Journal of Medicinal Chemistry. 63(8):3785.
2. Jang S., et al. 2021. ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance. Commun. Biol. 4:497.
3. Pro-cyclic dinucleotides and pro-cyclic dinucleotide conjugates for cytokine induction. WO 2019/129880A1 and foreign equivalents.
4. Fluorinated cyclic dinucleotides for cytokine induction, patent WO2016096174A1.
5. Cyclic dinucleotides for cytokine induction, patent US10011630B2 and foreign equivalents.

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