CRX-555   Click here for help

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
Immunopharmacology Ligand
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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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
References
1. Alderson MR, McGowan P, Baldridge JR, Probst P. (2006)
TLR4 agonists as immunomodulatory agents.
J Endotoxin Res, 12 (5): 313-9. [PMID:17059695]
2. Cluff CW, Baldridge JR, Stöver AG, Evans JT, Johnson DA, Lacy MJ, Clawson VG, Yorgensen VM, Johnson CL, Livesay MT et al.. (2005)
Synthetic toll-like receptor 4 agonists stimulate innate resistance to infectious challenge.
Infect Immun, 73 (5): 3044-52. [PMID:15845512]
3. Fort MM, Mozaffarian A, Stöver AG, Correia Jda S, Johnson DA, Crane RT, Ulevitch RJ, Persing DH, Bielefeldt-Ohmann H, Probst P et al.. (2005)
A synthetic TLR4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease.
J Immunol, 174 (10): 6416-23. [PMID:15879143]
4. Goriely S, De WD, Goldman M, Detienne S, Brulet J-M. (2008)
Aminoalkyl glucosamine phosphate compounds for treating autoimmune diseases.
Patent number: WO2008128997A1. Assignee: Universite Libre De Bruxelles. Priority date: 19/04/2007. Publication date: 30/10/2008.
5. Gregg KA, Harberts E, Gardner FM, Pelletier MR, Cayatte C, Yu L, McCarthy MP, Marshall JD, Ernst RK. (2018)
A lipid A-based TLR4 mimetic effectively adjuvants a Yersinia pestis rF-V1 subunit vaccine in a murine challenge model.
Vaccine, 36 (28): 4023-4031. [PMID:29861179]
6. Hawkins LD, Ishizaka ST, McGuinness P, Zhang H, Gavin W, DeCosta B, Meng Z, Yang H, Mullarkey M, Young DW et al.. (2002)
A novel class of endotoxin receptor agonists with simplified structure, toll-like receptor 4-dependent immunostimulatory action, and adjuvant activity.
J Pharmacol Exp Ther, 300 (2): 655-61. [PMID:11805229]
7. Huang LD, Lin HJ, Huang PH, Hsiao WC, Reddy LV, Fu SL, Lin CC. (2011)
Synthesis of serine-based glycolipids as potential TLR4 activators.
Org Biomol Chem, 9 (7): 2492-504. [PMID:21336404]
8. Johnson DA, Sowell CG. (2001)
Aminoalkyl glucosaminide phosphate compounds and their use as adjuvants and immunoeffectors.
Patent number: US6303347B1. Assignee: Corixa Corp.. Priority date: 08/05/1997. Publication date: 16/10/2001.
9. Stöver AG, Da Silva Correia J, Evans JT, Cluff CW, Elliott MW, Jeffery EW, Johnson DA, Lacy MJ, Baldridge JR, Probst P et al.. (2004)
Structure-activity relationship of synthetic toll-like receptor 4 agonists.
J Biol Chem, 279 (6): 4440-9. [PMID:14570885]
10. Zaffaroni L, Peri F. (2018)
Recent advances on Toll-like receptor 4 modulation: new therapeutic perspectives.
Future Med Chem, 10 (4): 461-476. [PMID:29380635]