apratastat   Click here for help

GtoPdb Ligand ID: 6482

Synonyms: compound 5h [PMID: 16426848] | TMI-05 | TMI005
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Apratastat (TMI-005) is an orally active dual TACE (ADAM17)/MMP13 inhibitor that was developed for the potential treatment of inflammation [2]. TACE = TNF α-converting enzyme, which is a well validated therapeutic target for the treatment of rheumatoid arthritis. Inhibition of MMP13 (a peptidase that preferentially degrades type II collagen and aggrecan) is relevant since this is predicted to prevent the degradation of cartilage in rheumatoid arthritis [1,4].
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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 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.

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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 149.85
Molecular weight 414.09
XLogP 0.93
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
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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.

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/)

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Canonical SMILES OCC#CCOc1ccc(cc1)S(=O)(=O)N1CCSC(C1C(=O)NO)(C)C
Isomeric SMILES OCC#CCOc1ccc(cc1)S(=O)(=O)N1CCSC([C@@H]1C(=O)NO)(C)C
InChI InChI=1S/C17H22N2O6S2/c1-17(2)15(16(21)18-22)19(9-12-26-17)27(23,24)14-7-5-13(6-8-14)25-11-4-3-10-20/h5-8,15,20,22H,9-12H2,1-2H3,(H,18,21)/t15-/m0/s1
InChI Key MAVDNGWEBZTACC-HNNXBMFYSA-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/)
References
1. Konttinen YT, Ainola M, Valleala H, Ma J, Ida H, Mandelin J, Kinne RW, Santavirta S, Sorsa T, López-Otín C et al.. (1999)
Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis.
Ann Rheum Dis, 58 (11): 691-7. [PMID:10531073]
2. Levin JI, Chen JM, Laakso LM, Du M, Schmid J, Xu W, Cummons T, Xu J, Jin G, Barone D et al.. (2006)
Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.
Bioorg Med Chem Lett, 16 (6): 1605-9. [PMID:16426848]
3. Thabet MM, Huizinga TW. (2006)
Drug evaluation: apratastat, a novel TACE/MMP inhibitor for rheumatoid arthritis.
Curr Opin Investig Drugs, 7 (11): 1014-9. [PMID:17117591]
4. Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y. (2000)
Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis.
Ann Rheum Dis, 59 (6): 455-61. [PMID:10834863]