CRX-527

CRX-527 activates TLR4

Synthetic lipid A analog - TLR4 agonist

CRX-527 is a synthetic lipid A mimic belonging to the aminoakyl glucoaminide 4-phosphate (AGP) family [1]. Similar to lipid A, the active component of lipopolysaccharide (LPS), CRX-527 activates Toll-like receptor 4 (TLR4).  Subsequently, it initiates MyD88- and TRIF-dependent pro-inflammatory signaling cascades. Importantly, CRX-527 does not require the TLR4 co-receptor CD14 for activation of either signaling pathway [2]. CRX-527, along with other AGPs, is less toxic than LPS and importantly retains its immunostimulatory properties. Therefore, AGPs have great potential as future vaccine adjuvants as well as stand‑alone immunostimulants [3].

CRX-527 is composed of a monosaccharide unit glycosidically linked to an L-serine-based aglycon unit. It is a hexa -acylated molecule consisting of three "primary" myristic (C14) and three decanoic (C10) acyl chains. Interestingly, most likely due to its structure CRX-527 does not activate a typical Limulus amebocyte lysate (LAL) assay commonly used for measuring endotoxin levels.

Key highlights of CRX-527:

• Highly specific and potent TLR4 agonist
• Displays significantly less toxicity when compared to LPS
• Doesn't require the co-receptor CD14 for TLR4 activation and signaling

InvivoGen's CRX-527 is of the highest quality, guaranteed free of bacterial contamination, and has been functionally validated on HEK-Blue™ hTLR4 cells.

References:

1. Stover, A.G. et al. 2003.Structure-activity relationship of synthetic Toll-like receptor 4 agonists. J. Biol. Chem. 279:4440-4449.
2. Legat, A.et al. 2010.CD14-independent responses induced by a synthetic lipid A mimetic. Eur. J. Immunol. 40:792-802.
3. Tan, Z.Y. et al. 2013. Synthetic TLR4 agonists as a potential immunotherapy for melioidosis. Open J Immunol. 3: 1-9.

Learn more about TLR4 and its co-receptors

Learn more about different Lipid A structures

Figures

HEK-Blue™ hTLR4 cells were incubated with increasing concentrations of CRX‑527 and synthetic monophosphoryl lipid A (MPLA). After overnight incubation in HEK-Blue™ detection medium, a SEAP detection growth medium, the activation of TLR4 was assessed by determining the presence of SEAP in the supernatant. Data are expressed as OD (λ=630nm) (±SEM).

Specifications

CAS Number: 216014-14-1

Formula: C₈₁H₁₅₁N₂O₁₉P

Molecular weight: 1488.07 g/mol

Endotoxin Level: >5 x 10⁴ EU/mg (measured using the HEK-Blue™ LPS detection kit II)

Solubility: 1 mg/ml in DMSO

Quality Control

• Purity: ≥90% (UHPLC)
• Activation of TLR4 by CRX-527 has been confirmed using a HEK Blue™ TLR4 cellular assay.
• Absence of bacterial contamination (e.g. lipoproteins) has been confirmed using a HEK-Blue™ TLR2 cellular assay.

Contents

• 1 mg CRX-527 (provided as a clear lipidic film)

CRX-527 is shipped at room temperature.

Store at -20°C. Upon resuspension, prepare aliquots of CRX-527 and store at -20°C.

Resuspended product is stable 6 months at -20°C. 

Avoid repeated freeze-thaw cycles.

Details

Chemical structure of CRX-527: