CWHM12   Click here for help

GtoPdb Ligand ID: 10495

Synonyms: CWHM 12 | CWHM-12
Compound class: Synthetic organic
Comment: CWHM12 is a pan αv integrin antagonist [1]. It was used to determine that αv integrin activation regulates fibrosis in models of organ fibrosis. These findings suggest that targeting all αv integrins may have clinical utility in the treatment of a broad range of fibrotic diseases. The S enantiomer of CWHM12 is the bioactive form; the R enantiomer does not inhibit any of the five αv-containing integrins in vitro.
Structurally, CWHM12 is a small-molecule RGD peptidomimetic antagonist in which the arginine (R) mimetic is a cyclic guanidino-substituted phenyl group and the aspartic acid (D) mimetic is a phenyl-substituted β amino acid. These two residues are linked by a glycine (G).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 10
Hydrogen bond donors 7
Rotatable bonds 12
Topological polar surface area 172.38
Molecular weight 589.15
XLogP 3.33
No. Lipinski's rules broken 1
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 OC1CNC(=NC1)Nc1cc(O)cc(c1)C(=O)NCC(=O)NC(c1cc(Br)cc(c1)C(C)(C)C)CC(=O)O
Isomeric SMILES OC1CNC(=NC1)Nc1cc(O)cc(c1)C(=O)NCC(=O)N[C@H](c1cc(Br)cc(c1)C(C)(C)C)CC(=O)O
InChI InChI=1S/C26H32BrN5O6/c1-26(2,3)16-4-14(5-17(27)8-16)21(10-23(36)37)32-22(35)13-28-24(38)15-6-18(9-19(33)7-15)31-25-29-11-20(34)12-30-25/h4-9,20-21,33-34H,10-13H2,1-3H3,(H,28,38)(H,32,35)(H,36,37)(H2,29,30,31)/t21-/m0/s1
InChI Key YDHAGPCZRFQPOI-NRFANRHFSA-N
References
1. Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG et al.. (2013)
Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs.
Nat Med, 19 (12): 1617-24. [PMID:24216753]