GtoPdb Ligand ID: 10091

Synonyms: CRX555 | N-[(3R)-3-(Octanoyloxy)myristoyl]-O-[2-[[(3R)-3-(octanoyloxy)myristoyl]amino]-3-O-[(3R)-3-(octanoyloxy)myristoyl]-4-O-phosphono-2-deoxy-beta-D-glucopyranosyl]-L-serine
Compound class: Synthetic organic
Comment: CRX-555 is a synthetic Toll-like receptor 4 (TLR4) partial agonist from the Corixa Corporation [9]. It is one of a series of lipid A mimetic aminoalkyl glucosaminide phosphate compounds that were synthesised with different length secondary acyl chains. CRX-555 has 8 carbon atoms in each of its 3 secondary acyl chains. The chemical structures for aminoalkyl glucosaminide phosphate lipid A mimetics including CRX-555 were originally claimed in patent US6303347B1 (now expired) TLR4 as potential adjuvants and immunoeffectors [8]. A later patent (WO2008128997A1 [4]) claims these compounds for prophylactic and therapeutic applications in autoimmune diseases. The partial agonist effect of CRX-555 was demonstrated in HeLa cells transfected with TLR4/MD-2/CD14 and an IL-8 luciferase promoter construct. While CRX-527 gave a maximum stimulation of almost 60-fold (at 10μg/ml), the maximum stimulation by CRX-555 at this concentration was only ~25-fold [9].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 21
Hydrogen bond donors 6
Rotatable bonds 73
Topological polar surface area 315.96
Molecular weight 1402.97
XLogP 22.5
No. Lipinski's rules broken 4
InChI InChI=1S/C75H139N2O19P/c1-7-13-19-25-28-31-34-40-43-49-60(91-67(81)52-46-37-22-16-10-4)55-65(79)76-63(74(85)86)59-90-75-71(77-66(80)56-61(92-68(82)53-47-38-23-17-11-5)50-44-41-35-32-29-26-20-14-8-2)73(72(64(58-78)94-75)96-97(87,88)89)95-70(84)57-62(93-69(83)54-48-39-24-18-12-6)51-45-42-36-33-30-27-21-15-9-3/h60-64,71-73,75,78H,7-59H2,1-6H3,(H,76,79)(H,77,80)(H,85,86)(H2,87,88,89)/t60-,61-,62-,63+,64-,71-,72-,73-,75-/m1/s1
Bioactivity Comments
CRX-555 and other aminoalkyl glucosaminide phosphate compounds from the series with ≤9-carbon secondary acyl chains do not elicit TNFα production from human monocyte-derived macrophages, but it does induce transcriptional activation of eight genes on a custom microarray of ~300 inflammatory target genes [9]. In contrast, CRX-527 which has 10-carbon secondary acyl chains potently activates TNFα production and transcriptional responses (68 genes) in the same assays.
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
TLR4 Hs Agonist Partial agonist - - - 9