compound 8 [PMID: 25898023]   Click here for help

GtoPdb Ligand ID: 10498

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 8 [PMID: 25898023] is a selective inhibitor of Rho kinase (ROCK) activity that was developed for the treatment of ocular inflammation [1]. In an effort to reduce unintended systemic ROCK-associated side effects and maximise local effects, it was designed to be rapidly converted to an inactive metabolite in the systemic circulation. Compounds of this type are known as 'soft' drugs. Specifically, compound 8 contains an ester group that is hydrolysed by blood esterases to an inactive carboxylic acid metabolite (8M).
Amakem Ophthalmics have a 'soft' ROCK inhibitor AMA0076 that has been shown to reduce intraocular pressure in a rabbit model of glaucoma [4], and which has completed Phase 2 clinical evaluation in glaucoma/ocular hypertension (NCT01693315). The structure of AMA0076 has not been formally disclosed, but it appears to be derived from the same chemical scaffold as compound 8.
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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 8
Hydrogen bond donors 3
Rotatable bonds 10
Topological polar surface area 123.41
Molecular weight 498.17
XLogP 3.87
No. Lipinski's rules broken 0
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 NCc1ccc(cc1c1cccc(c1)C(=O)Nc1ccc(cc1)C(=O)OC)C(=O)Nc1ccncc1F
Isomeric SMILES NCc1ccc(cc1c1cccc(c1)C(=O)Nc1ccc(cc1)C(=O)OC)C(=O)Nc1ccncc1F
InChI InChI=1S/C28H23FN4O4/c1-37-28(36)17-7-9-22(10-8-17)32-26(34)19-4-2-3-18(13-19)23-14-20(5-6-21(23)15-30)27(35)33-25-11-12-31-16-24(25)29/h2-14,16H,15,30H2,1H3,(H,32,34)(H,31,33,35)
InChI Key MXWDBTLNBKIMEX-UHFFFAOYSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
methyl 4-[[3-[2-(aminomethyl)-5-[(3-fluoropyridin-4-yl)carbamoyl]phenyl]benzoyl]amino]benzoate
Database Links Click here for help
BindingDB Ligand 50087131
ChEMBL Ligand CHEMBL3426624
GtoPdb PubChem SID 387065580
PubChem CID 71283262
Search Google for chemical match using the InChIKey MXWDBTLNBKIMEX-UHFFFAOYSA-N
Search Google for chemicals with the same backbone MXWDBTLNBKIMEX
UniChem Compound Search for chemical match using the InChIKey MXWDBTLNBKIMEX-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey MXWDBTLNBKIMEX-UHFFFAOYSA-N