CRX-555   

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
SMILES / InChI / InChIKey
Canonical SMILES CCCCCCCCCCCC(CC(=O)NC1C(OCC(C(=O)O)NC(=O)CC(OC(=O)CCCCCCC)CCCCCCCCCCC)OC(C(C1OC(=O)CC(OC(=O)CCCCCCC)CCCCCCCCCCC)OP(=O)(O)O)CO)OC(=O)CCCCCCC
Isomeric SMILES CCCCCCCCCCC[C@H](CC(=O)N[C@H]1[C@H](OC[C@@H](C(=O)O)NC(=O)C[C@H](OC(=O)CCCCCCC)CCCCCCCCCCC)O[C@@H]([C@H]([C@@H]1OC(=O)C[C@H](OC(=O)CCCCCCC)CCCCCCCCCCC)OP(=O)(O)O)CO)OC(=O)CCCCCCC
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
InChI Key WNFNQTGQGFHQLU-NRBIUWCVSA-N
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
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
TLR4 Hs Agonist Partial agonist - - - 9
[9]