apicidin   Click here for help

GtoPdb Ligand ID: 7495

Synonyms: OSI-2040
Antimalarial Ligand
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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2D Structure
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Physico-chemical Properties
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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
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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
Bioactivity Comments
Apicidin has in vitro activity against P. falciparum (strain Dd2, MIC of 125 ng/ml) and other species of apicomplexan parasite (MIC of 4-62 ng/ml) [2]. This activity is likely to be due to potent inhibition of histone deacetylase (E. tenella histone deacetylase, IC50 of 4nM) [2].
Selectivity at enzymes
Key to terms and symbols Click on species/strain names for details Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
histone deacetylase 1 Hs Inhibitor Inhibition 10.4 pKi - 1
pKi 10.4 (Ki 4x10-11 M) [1]
histone deacetylase 2 Hs Inhibitor Inhibition 9.9 pKi - 1
pKi 9.9 (Ki 1.2x10-10 M) [1]
histone deacetylase 3 Hs Inhibitor Inhibition 9.6 pKi - 1
pKi 9.6 (Ki 2.6x10-10 M) [1]
histone deacetylase 8 Hs Inhibitor Inhibition 7.3 pKi - 1
pKi 7.3 (Ki 4.9x10-8 M) [1]
histone deacetylase 3 Hs Inhibitor Inhibition 7.4 – 7.5 pEC50 - 4
pEC50 7.5 (EC50 3x10-8 M) [4]
pEC50 7.4 (EC50 4.3x10-8 M) [4]
histone deacetylase 2 Hs Inhibitor Inhibition 6.9 pEC50 - 4
pEC50 6.9 (EC50 1.2x10-7 M) [4]
histone deacetylase 8 Hs Inhibitor Inhibition 6.2 pEC50 - 4
pEC50 6.2 (EC50 5.75x10-7 M) [4]