IAXO-101 (CD14/TLR4 Antagonist) (synthetic)
|Synonyms||Methyl 6-deoxy-6-N-dimethyl-N-cyclopentylammonium-2,3-di-O-tetradecyl-α-D-glucopyranoside iodide|
|MW||810.02g/mol (iodide salt)|
|Purity Chemicals||≥98% (TLC)|
|Solubility||Soluble in Methanol, DMSO and Ethanol 1:1 (vol:vol): >10mM.|
Described to interfere with human, rat and mouse TLR4/CD14 signaling, other species not tested. Optimal working concentration depends upon the type, purity and concentration and of TLR4 ligand, carrier protein such as LPS-binding protein (LBP), soluble and membrane-bound CD14, the presence of TLR4 co-receptors (e.g. CD36) as well as on type and time of read-out (e.g. cytokine measurement in cell culture supernatant) or the biological outcome of in vivo experiments and therefore needs to be determined for each application. Recommended starting concentration: in vitro: 5μM, in vivo (rodent): 3mg/kg.
|Identity||Determined by NMR and MS.|
|Declaration||Manufactured by Innaxon.|
|Other Product Data||
Reconstitution: For a 2mM stock solution, dissolve total vial content in 617μl (1mg size) or 3,085μl (5mg size) DMSO/Ethanol (1:1) (vol:vol).
|Shipping and Handling|
|Short Term Storage||+4°C|
|Long Term Storage||+4°C|
|Use/Stability||Stable for at least 1 year after receipt when stored at +4°C.|
|Product Specification Sheet|
- CD14/TLR4 antagonist. Inhibitor of sterile inflammation.
- Synthetic TLR4/CD14 ligand with TLR4 modulating activities in vitro, and conferring protection against TLR4/CD14-mediated tissue damage and inflammation in vivo. Useful to explore CD14- dependent and TLR4-independent pathways and TLR4 activation by endogenous ligands (e.g. hyaluronic acid oligosaccharides, oxLDL, HMGB1) in sterile inflammation. Shown to inhibit neuropathic pain, secondary necrosis of acute drug-induced liver failure and vascular inflammation, and abdominal aortic aneurysm by blocking non-hematopoietic TLR4 signaling. Useful tool, where inhibition of sterile (auto-) inflammation is desired, without compromising TLR4’s key role in the defense of pathogens.
- Inhibition of lipid a stimulated activation of human dendritic cells and macrophages by amino and hydroxylamino monosaccharides: F. Peri, et al.; Angew. Chem.46, 3308 (2007)
- TLR4 receptor as new target to treat neuropathic pain: efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice: I. Bettoni, et al.; Glia 56, 1312 (2008)
- Glycolipids and benzylammonium lipids as novel antisepsis agents: synthesis and biological characterization: M. Piazza, et al.; J. Med. Chem. 52, 1209 (2009)
- Evidence of a specific interaction between new synthetic antisepsis agents and CD14: M. Piazza, et al.; Biochemistry 48, 12337 (2009)
- Exploring the LPS/TLR4 signal pathway with small molecules: F. Peri, et al.; Biochem. Soc. Trans. 38, 1390 (2010) (Review)
- Therapeutic targeting of innate immunity with Toll-like receptor 4 (TLR4) antagonists: F. Peri & M. Piazza; Biotechnol. Adv. 30, 251 (2012) (Review)
- Synthetic molecules and functionalized nanoparticles targeting the LPS-TLR4 signaling: A new generation of immunotherapeutics: F. Peri, et al.; Pure Appl. Chem. 84, 97 (2012) (Review)
- Toll like receptor 4 antagonist prevents acetaminophen induced acute liver failure in mice: a novel therapeutic strategy: N. Shah, et al.; Gut 61, A28 (2012)
- Multivalent glycoconjugates as anti-pathogenic agents. A. Bernardi, et al.; Chem. Soc. Rev. 42, 4709 (2013) (Review)
- Toll-like receptor 4 (TLR4) modulation by synthetic and natural compounds: an update: F. Peri & V. Calabrese; Med. Chem. 57, 3612 (2014) (Review)
- TLR4-mediated placental pathology and pregnancy outcome in experimental Malaria: R. Barboza, et al.; Sci. Rep. 7, 8623 (2017)
- TLR4/NF-kB axis induces fludarabine resistance by suppressing TXNIP expression in acute myeloid leukemia cells: H. Huy, et al.; BBRC in press, (2018)
- Targeting CD14 on blood derived cells improves intracortical microelectrode performance: H.W. Bedell, et al.; Biomaterials 163, 163 (2018)
- Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance: J.K. Hermann, et al.; J. Neural Eng. 15, 025002 (2018)
- Effect of CD14/TLR4 antagonist on GnRH/LH secretion in ewe during central inflammation induced by intracerebroventricular administration of LPS: K. Haziak, et al.; J. Animal Sci. Biotech. 9, 52 (2018)