compound 51 [Mallinger et al., 2016]   Click here for help

GtoPdb Ligand ID: 9170

Compound class: Synthetic organic
Comment: Compound 51 is a potent and selective CDK8/19 inhibitor [3]. It is one of the compounds claimed in patent WO2016009076 [4]. Compound 51 hasa similar inhibitory potency as CCT251545, but is built on a modified chemical scaffold [3]. This is a type I inhibitor, binding in a DMG-in mode.
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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 7
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 99.16
Molecular weight 414.18
XLogP 2.43
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 COC1CN(C1)C(=O)c1ccc2c(n1)c(cnc2N)c1ccc(cc1)c1cnn(c1)C
Isomeric SMILES COC1CN(C1)C(=O)c1ccc2c(n1)c(cnc2N)c1ccc(cc1)c1cnn(c1)C
InChI InChI=1S/C23H22N6O2/c1-28-11-16(9-26-28)14-3-5-15(6-4-14)19-10-25-22(24)18-7-8-20(27-21(18)19)23(30)29-12-17(13-29)31-2/h3-11,17H,12-13H2,1-2H3,(H2,24,25)
InChI Key OJIQEAIHEGJBFE-UHFFFAOYSA-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. Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S et al.. (2008)
CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity.
Nature, 455 (7212): 547-51. [PMID:18794900]
2. Kapoor A, Goldberg MS, Cumberland LK, Ratnakumar K, Segura MF, Emanuel PO, Menendez S, Vardabasso C, Leroy G, Vidal CI et al.. (2010)
The histone variant macroH2A suppresses melanoma progression through regulation of CDK8.
Nature, 468 (7327): 1105-9. [PMID:21179167]
3. Mallinger A, Schiemann K, Rink C, Sejberg J, Honey MA, Czodrowski P, Stubbs M, Poeschke O, Busch M, Schneider R et al.. (2016)
2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19.
ACS Med Chem Lett, 7 (6): 573-8. [PMID:27326329]
4. Schiemann K, Blagg J, Mallinger A, Rink C, Sejberg J, Honey M. (2016)
Novel naphthryidines and isoquinolines and their use as cdk8/19 inhibitors.
Patent number: WO2016009076. Assignee: Merck Patent Gmbh, Cancer Research Technology Limited. Priority date: 17/07/2014. Publication date: 21/01/2016.