UNC0321   Click here for help

GtoPdb Ligand ID: 8389

Synonyms: UNC 0321 | UNC-0321
Compound class: Synthetic organic
Comment: UNC0321 was the first reported picomolar inhibitor of the histone methyltransferase, G9a (eq. euchromatic histone-lysine N-methyltransferase 2, EHMT2) [3]. G9a catalyses methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of the tumour suppressor, p53 [1], and is reported to be overexpressed in human cancers.
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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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Click here for structure editor
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 1
Rotatable bonds 11
Topological polar surface area 78.46
Molecular weight 515.36
XLogP 2.14
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 COc1cc2c(cc1OCCOCCN(C)C)nc(nc2NC1CCN(CC1)C)N1CCCN(CC1)C
Isomeric SMILES COc1cc2c(cc1OCCOCCN(C)C)nc(nc2NC1CCN(CC1)C)N1CCCN(CC1)C
InChI InChI=1S/C27H45N7O3/c1-31(2)15-16-36-17-18-37-25-20-23-22(19-24(25)35-5)26(28-21-7-11-33(4)12-8-21)30-27(29-23)34-10-6-9-32(3)13-14-34/h19-21H,6-18H2,1-5H3,(H,28,29,30)
InChI Key AULLUGALUBVBDD-UHFFFAOYSA-N
References
1. Huang J, Dorsey J, Chuikov S, Pérez-Burgos L, Zhang X, Jenuwein T, Reinberg D, Berger SL. (2010)
G9a and Glp methylate lysine 373 in the tumor suppressor p53.
J Biol Chem, 285 (13): 9636-41. [PMID:20118233]
2. Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR, Issa JP. (2008)
Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells.
PLoS ONE, 3 (4): e2037. [PMID:18446223]
3. Liu F, Chen X, Allali-Hassani A, Quinn AM, Wigle TJ, Wasney GA, Dong A, Senisterra G, Chau I, Siarheyeva A et al.. (2010)
Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines.
J Med Chem, 53 (15): 5844-57. [PMID:20614940]
4. McGarvey KM, Fahrner JA, Greene E, Martens J, Jenuwein T, Baylin SB. (2006)
Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state.
Cancer Res, 66 (7): 3541-9. [PMID:16585178]
5. Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H et al.. (2002)
G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis.
Genes Dev, 16 (14): 1779-91. [PMID:12130538]