apicidin   Click here for help

GtoPdb Ligand ID: 7495

Synonyms: OSI-2040
Antimalarial Ligand
Compound class: Natural product or derivative
Comment: Acipidin is a natural product fungal metabolite [2]. It inhibits cancer cell proliferation [3], via histone deacetylase (HDAC) inhibition.

The compound has broad-spectrum activity against apicomplexan parasites including Plasmodium species [2]. The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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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 9
Hydrogen bond donors 3
Rotatable bonds 12
Topological polar surface area 138.84
Molecular weight 623.37
XLogP 4.24
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 CCC(=O)CCCCCC1NC(=O)C2CCCCN2C(=O)C(NC(=O)C(NC1=O)Cc1cn(c2c1cccc2)OC)C(CC)C
Isomeric SMILES CCC(=O)CCCCC[C@@H]1NC(=O)[C@H]2CCCCN2C(=O)[C@@H](NC(=O)[C@@H](NC1=O)Cc1cn(c2c1cccc2)OC)[C@H](CC)C
InChI InChI=1S/C34H49N5O6/c1-5-22(3)30-34(44)38-19-13-12-18-29(38)33(43)35-26(16-9-7-8-14-24(40)6-2)31(41)36-27(32(42)37-30)20-23-21-39(45-4)28-17-11-10-15-25(23)28/h10-11,15,17,21-22,26-27,29-30H,5-9,12-14,16,18-20H2,1-4H3,(H,35,43)(H,36,41)(H,37,42)/t22-,26-,27-,29+,30-/m0/s1
InChI Key JWOGUUIOCYMBPV-GMFLJSBRSA-N
References
1. Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R. (2010)
Chemical phylogenetics of histone deacetylases.
Nat Chem Biol, 6 (3): 238-243. [PMID:20139990]
2. Darkin-Rattray SJ, Gurnett AM, Myers RW, Dulski PM, Crumley TM, Allocco JJ, Cannova C, Meinke PT, Colletti SL, Bednarek MA et al.. (1996)
Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase.
Proc Natl Acad Sci USA, 93 (23): 13143-7. [PMID:8917558]
3. Han JW, Ahn SH, Park SH, Wang SY, Bae GU, Seo DW, Kwon HK, Hong S, Lee HY, Lee YW et al.. (2000)
Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin.
Cancer Res, 60 (21): 6068-74. [PMID:11085529]
4. Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Berghs SC, Carey N et al.. (2008)
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors.
Biochem J, 409 (2): 581-9. [PMID:17868033]