ONX-0801   Click here for help

GtoPdb Ligand ID: 9590

Synonyms: BGC 945 | BGC-945 | N-[4-[2-Propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-d-glutamic acid 1 [3] | ONX 0801
PDB Ligand
Compound class: Synthetic organic
Comment: ONX-0801 (originally named BGC 945) is a first-in-class small molecule inhibitor of thymidylate synthase (TS), that has been designed to accumulate differentially in cancer cells overexpressing the α-folate receptor [3] (FOLR1; P15328). Functionally, it resembles the TS inhibitors plevitrexed and raltitrexed. ONX-0801 is an oncology drug lead for epithelial tumours such as ovarian [1], lung and endometrial cancers, and mesothelioma tumours.
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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 14
Hydrogen bond donors 7
Rotatable bonds 17
Topological polar surface area 239.32
Molecular weight 647.22
XLogP 2.08
No. Lipinski's rules broken 3
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 C#CCN(C1CCc2c1cc1c(=O)nc([nH]c1c2)CO)c1ccc(cc1)C(=O)NC(C(=O)O)CCC(=O)NC(C(=O)O)CCC(=O)O
Isomeric SMILES C#CCN([C@H]1CCc2c1cc1c(=O)nc([nH]c1c2)CO)c1ccc(cc1)C(=O)N[C@H](C(=O)O)CCC(=O)N[C@@H](C(=O)O)CCC(=O)O
InChI InChI=1S/C32H33N5O10/c1-2-13-37(25-10-5-18-14-24-21(15-20(18)25)30(43)36-26(16-38)33-24)19-6-3-17(4-7-19)29(42)35-23(32(46)47)8-11-27(39)34-22(31(44)45)9-12-28(40)41/h1,3-4,6-7,14-15,22-23,25,38H,5,8-13,16H2,(H,34,39)(H,35,42)(H,40,41)(H,44,45)(H,46,47)(H,33,36,43)/t22-,23+,25+/m1/s1
InChI Key NVHRBQOZEMFKLD-CUYJMHBOSA-N
References
1. Campbell IG, Jones TA, Foulkes WD, Trowsdale J. (1991)
Folate-binding protein is a marker for ovarian cancer.
Cancer Res, 51 (19): 5329-38. [PMID:1717147]
2. Gibbs DD, Theti DS, Wood N, Green M, Raynaud F, Valenti M, Forster MD, Mitchell F, Bavetsias V, Henderson E et al.. (2005)
BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors.
Cancer Res, 65 (24): 11721-8. [PMID:16357184]
3. Tochowicz A, Dalziel S, Eidam O, O'Connell 3rd JD, Griner S, Finer-Moore JS, Stroud RM. (2013)
Development and binding mode assessment of N-[4-[2-propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-D-glutamic acid (BGC 945), a novel thymidylate synthase inhibitor that targets tumor cells.
J Med Chem, 56 (13): 5446-55. [PMID:23710599]