ADP-Heptose (L-isomer) - ALPK1 ligand

Synthetic ADP-L-Heptose

ABOUT

ALPK1-TIFA inducer – ADP-Heptose

Bacterial ADP-heptose is an intermediary sugar in the biosynthesis of lipopolysaccharide (LPS), an essential component of the outer membrane of Gram-negative bacteria. ADP-heptose acts as a pathogen-associated molecular pattern (PAMP) that is sensed in the host cell cytosol by the innate immune receptor ALPK1. Upon ALPK1 engagement, ADP-heptose triggers phosphorylation and oligomerization of the adaptor protein TIFA, followed by recruitment of TRAF6. This signaling cascade ultimately leads to NF-κB activation and the induction of a strong pro-inflammatory immune response (see figure).

More details

InvivoGen has synthesized and provides ADP-L-Heptose for the study of ALPK1-dependent immune signaling. It is of the highest quality, guaranteed free of bacterial contamination, and has been functionally validated on HEK-Blue™ Null1-v cells. Additionally, to foster research into ADP-Heptose-dependent signaling, InvivoGen provides HEK-Blue™ KO-ALPK1 & HEK-Blue™ KO-TIFA cells (see figure). In addition, to support studies requiring enhanced stability and potency, InvivoGen also offers UD(PS)-L-Heptose, a phosphorothioate-modified analogue of ADP-L-Heptose.

Key features:

  • Potent LPS-intermediary metabolite produced by all Gram-negative bacteria
  • Activates the cytosolic ALPK1-TIFA signaling pathway
  • Easily penetrates the cell wall for delivery to the host cell cytoplasm
 

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

ADP-L-Heptose induced ALPK1-TIFA signaling
ADP-L-Heptose induced ALPK1-TIFA signaling

SPECIFICATIONS

Specifications

Source
Synthetic
Target

ALPK1

Chemical formula

C17H27N5O16P2 . Et3NH (stable form)

Molecular weight
720.21 g/mol (stable form)
Working concentration

30 - 300 ng/ml for cellular assays

Purity
> 95% (UHPLC)
Solubility

10 mg/ml in H2O

Appearance (form)
Dried powder
Reconstitution buffer
Endotoxin-free water (provided)
Endotoxin

< 1 EU/mg (measurement by kinetic chromogenic LAL assay)

Tested applications

Cellular assays

Quality control

Each lot is functionally tested and validated.

CONTENTS

Contents

  • Product: 
    ADP-L-Heptose
  • Cat code: 
    tlrl-adph-l
  • Quantity: 
    250 µg
Includes:

1.5 ml of endotoxin-free water

Shipping & Storage

  • Shipping method:  Room temperature

    • Storage:

    • Upon receipt, store product at -20 °C.
    Stability: The resuspended product is stable for at least 3 months at -20°C

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

ADP-heptose signaling

ADP-heptose is a conserved intracellular metabolite produced by Gram-negative bacteria during lipopolysaccharide (LPS) core biosynthesis. Independent studies in Helicobacter pylori and Shigella flexneri first identified ADP-heptose as a previously unrecognized pathogen-associated molecular pattern (PAMP) capable of triggering host innate immune responses [1,2]. Unlike classical PAMPs detected at the cell surface or within endosomal compartments, ADP-heptose is sensed within the host cell cytosol, highlighting a distinct mode of immune surveillance directed against bacterial metabolic intermediates.

The cytosolic receptor alpha kinase 1(ALPK1) has been identified as the innate immune sensor for bacterial ADP-heptose [3]. Upon cytosolic entry, ADP-heptose directly engages ALPK1, leading to activation of its kinase function. Activated ALPK1 phosphorylates the adaptor protein TRAF-interacting protein with forkhead-associated domain (TIFA), promoting its oligomerization and subsequent recruitment of TNF receptor–associated factor 6 (TRAF6). This signaling complex initiates downstream activation of NF-κB pathway, resulting in rapid transcription of pro-inflammatory cytokines and chemokines [3].

Role of ADP-heptose–ALPK1 signaling in immunity

Activation of the ALPK1–TIFA axis by ADP-heptose plays a central role in antibacterial host defense by amplifying inflammatory signaling and coordinating immune cell recruitment. Beyond infection, emerging evidence indicates that this pathway contributes more broadly to immune regulation, including inflammatory responses associated with cancer [4]. By linking bacterial metabolic activity to cytosolic innate immune signaling, ADP-heptose–dependent ALPK1 activation represents a unique immunological axis at the intersection of microbial sensing, inflammation, and disease pathogenesis [3].

 

References:

1. Pfannkuch L. et al., 2019. ADP heptose, a novel pathogen-associated molecular pattern identified in Helicobacter pylori. FASEB J, fj201802555R.
2. Garcia-Weber D. et al., 2018. ADP-heptose is a newly identified pathogen-associated molecular pattern of Shigella flexneri. EMBO Rep 19.
3. Zhou, P. et al. 2018. Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. Nature 561, 122-126.
4. Tian X. et al., 2025.. Agonists for cytosolic bacterial receptor ALPK1 induce antitumour immunity. Nature.
 

 

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