IAXO-102 (CD14/TLR4 Antagonist) (synthetic)
|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 853μl (1mg size) or 4,266μl (5mg size) in (1:1) DMSO/Ethanol (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)
- A novel small mimetic molecule TLR4 antagonist (IAXO-102) modulates TLR4 proinflammatory signalling and inhibits aortic aneurysms development: C. Huggins, et al.; Atherosclerosis 241, e53 (2015)
- Effects of Toll-Like Receptor 4 antagonists against cerebral vasospasm after experimental subarachnoid hemorrhage in mice: F. Kawakita, et al.; Mol. Neurobiol. 54, 6624 (2017)
- Selective Toll-Like Receptor 4 antagonists prevent acute blood-brain barrier disruption after subarachnoid hemorrhage in mice: T. Okada, et al.; Mol. Neurobiol. 56, 976 (2019)
- Cancer-derived VEGF-C increases chemokine production in lymphatic endothelial cells to promote CXCR2-dependent cancer invasion and MDSC recruitment: J.Y. Chen, et al.; Cancers 11, 1120 (2019)
- Increasing the chemical variety of small-molecule-based TLR4 modulators: An Overview: A. Romerio & F. Peri; Front. Immunol. 11, 1210 (2020)
- Targeting TLR4-dependent inflammation in post-hemorrhagic brain injury: J.K. Karimy, et al.; Exp. Opin. Ther. Targets 24, 525 (2020) (Review)
- Platelets to surrogate lung inflammation in COVID-19 patients: H.K. Bhotla, et al.; Medic. Hypothes. 143, 110098 (2020)