uracil 20   Click here for help

GtoPdb Ligand ID: 9901

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Uracil 20 is a small molecule caspase-1 inhibitor that was developed as a topically active anti-inflammatory agent for the treatment of inflammatory acne [1]. This compound contrasts with the caspase -1 inhibitors belnacasan and pralnacasan which were designed for systemic exposure.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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.

✖
Hydrogen bond acceptors 10
Hydrogen bond donors 4
Rotatable bonds 10
Topological polar surface area 160.76
Molecular weight 611.24
XLogP 4.84
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES O=C1OC(C(C1)NC(=O)C1(CC1)n1c(=O)c(NC(=O)c2ccc(cc2C)Nc2ccc3c(c2)cccc3)cn(c1=O)C(C)C)O
Isomeric SMILES O=C1OC([C@H](C1)NC(=O)C1(CC1)n1c(=O)c(NC(=O)c2ccc(cc2C)Nc2ccc3c(c2)cccc3)cn(c1=O)C(C)C)O
InChI InChI=1S/C33H33N5O7/c1-18(2)37-17-26(29(41)38(32(37)44)33(12-13-33)31(43)36-25-16-27(39)45-30(25)42)35-28(40)24-11-10-22(14-19(24)3)34-23-9-8-20-6-4-5-7-21(20)15-23/h4-11,14-15,17-18,25,30,34,42H,12-13,16H2,1-3H3,(H,35,40)(H,36,43)/t25-,30?/m0/s1
InChI Key BTGMTHBOODBMHN-SUHMBNCMSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Immunopharmacology Comments
Inhibition of caspase-1 is an attractive mechanism for the development of novel therapeutics for the treatment of inflammatory diseases [2]. Caspase-1 inhibitors decrease conversion of pro-IL-1β to active and pro-inflammatory IL-1β. Inhibition of caspase-1 by small molecules is a strategy developed as an alternative to the use of anti-IL-1β neutralising antibodies, such as canakinumab, or the dimeric fusion protein rilonacept that acts as an IL-1β trap.