cenisertib   Click here for help

GtoPdb Ligand ID: 9927

Synonyms: AS-703569 | AS703569 [1] | compound 2 [PMID: 22695126] | compound 60a [WO2005118544A2] | enantiomer E1 [WO2005118544A2] | R-763 | R763
Compound class: Synthetic organic
Comment: Cenisertib is an Aurora kinase A/B inhibitor that was developed for anti-cancer potential [1]. We show the compound with chirality as specified by the IUPAC name submitted to the WHO for INN registration. It is compound 60a as claimed in patent WO2005118544A2 [3].
Cenisertib has improved aqueous solubility compared to the dual inhibitor ABT-348 (ilorasertib). Preclinical anti-proliferative efficacy of cenisertib has been demonstrated in a wide range of xenograft models [4] and cell lines [2].
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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 8
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 99.41
Molecular weight 451.25
XLogP 2.35
No. Lipinski's rules broken 0
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 CN1CCN(CC1)c1ccc(cc1C)Nc1ncc(c(n1)NC1C2C=CC(C1C(=O)N)C2)F
Isomeric SMILES CN1CCN(CC1)c1ccc(cc1C)Nc1ncc(c(n1)N[C@@H]1[C@H]2C=C[C@@H]([C@@H]1C(=O)N)C2)F
InChI InChI=1S/C24H30FN7O/c1-14-11-17(5-6-19(14)32-9-7-31(2)8-10-32)28-24-27-13-18(25)23(30-24)29-21-16-4-3-15(12-16)20(21)22(26)33/h3-6,11,13,15-16,20-21H,7-10,12H2,1-2H3,(H2,26,33)(H2,27,28,29,30)/t15-,16+,20+,21-/m1/s1
InChI Key KSOVGRCOLZZTPF-QMKUDKLTSA-N
References
1. Curtin ML, Heyman HR, Frey RR, Marcotte PA, Glaser KB, Jankowski JR, Magoc TJ, Albert DH, Olson AM, Reuter DR et al.. (2012)
Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases.
Bioorg Med Chem Lett, 22 (14): 4750-5. [PMID:22695126]
2. Illert AL, Seitz AK, Rummelt C, Kreutmair S, Engh RA, Goodstal S, Peschel C, Duyster J, von Bubnoff N. (2014)
Inhibition of Aurora kinase B is important for biologic activity of the dual inhibitors of BCR-ABL and Aurora kinases R763/AS703569 and PHA-739358 in BCR-ABL transformed cells.
PLoS ONE, 9 (11): e112318. [PMID:25426931]
3. Li H, Argade A, Singh R, Thota S, Carroll D, Tso K, Taylor V, Mclaughlin J, Markovstov VMV. (2005)
Cycloalkyl substituted pyrimidinediamine compounds and their uses.
Patent number: WO2005118544A2. Assignee: Rigel Pharmaceuticals, Inc.. Priority date: 18/05/2004. Publication date: 15/12/2005.
4. McLaughlin J, Markovtsov V, Li H, Wong S, Gelman M, Zhu Y, Franci C, Lang D, Pali E, Lasaga J et al.. (2010)
Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen.
J Cancer Res Clin Oncol, 136 (1): 99-113. [PMID:19609559]