peposertib   Click here for help

GtoPdb Ligand ID: 9766

Synonyms: example 136 [WO2014183850] | M3814 | MSC2490484A | nedisertib (deleted INN)
PDB Ligand
Compound class: Synthetic organic
Comment: Peposertib (M-3814) is an orally available inhibitor of DNA-dependent protein kinase (DNA-PK), that is being investiated for potential antineoplastic activity [3]. Experimental evidence indicates that M-3814 potentiates the effect of radiotherapy in several xenotransplanted human tumour types [1], an effect that is being evaluated in human cancer patients in a clinical trial. The compound is claimed as example 136 in patent WO2014183850 [2].
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 93.49
Molecular weight 481.13
XLogP 3.24
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES COc1ccc(nn1)C(c1cc(c(cc1Cl)F)c1ncnc2c1ccc(c2)N1CCOCC1)O
Isomeric SMILES COc1ccc(nn1)[C@H](c1cc(c(cc1Cl)F)c1ncnc2c1ccc(c2)N1CCOCC1)O
InChI InChI=1S/C24H21ClFN5O3/c1-33-22-5-4-20(29-30-22)24(32)16-11-17(19(26)12-18(16)25)23-15-3-2-14(10-21(15)27-13-28-23)31-6-8-34-9-7-31/h2-5,10-13,24,32H,6-9H2,1H3/t24-/m0/s1
InChI Key MOWXJLUYGFNTAL-DEOSSOPVSA-N
References
1. Damstrup L, Zimmerman A, Sirrenberg C, Zenke F, Vassilev L. (2016)
M3814, a DNA-dependent Protein Kinase Inhibitor (DNA-PKi), Potentiates the Effect of Ionizing Radiation (IR) in Xenotransplanted Tumors in Nude Mice.
Radiat Oncol, 94 (4): 940–941. DOI: 10.1016/j.ijrobp.2015.12.268
2. Fuchss T, Ulrich E, Buchstakker H-P, Werner M. (2016)
Arylquinazolines.
Patent number: WO2014183850. Assignee: Merck Patent Gmbh. Priority date: 11/05/2013. Publication date: 24/03/2016.
3. Harnor SJ, Brennan A, Cano C. (2017)
Targeting DNA-Dependent Protein Kinase for Cancer Therapy.
ChemMedChem, 12 (12): 895-900. [PMID:28423228]
4. Klein C, Dokic I, Mairani A, Mein S, Brons S, Häring P, Haberer T, Jäkel O, Zimmermann A, Zenke F et al.. (2017)
Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation.
Radiat Oncol, 12 (1): 208. [PMID:29287602]