DS-437   Click here for help

GtoPdb Ligand ID: 8395

Synonyms: DS437
Compound class: Synthetic organic
Comment: DS-437 is reported as a dual inhibitor of the protein arginine methyltransferases PRMT7 and PRMT5 [3].
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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 10
Hydrogen bond donors 5
Rotatable bonds 9
Topological polar surface area 185.74
Molecular weight 397.15
XLogP -0.6
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 CCNC(=O)NCCSCC1OC(C(C1O)O)n1cnc2c1ncnc2N
Isomeric SMILES CCNC(=O)NCCSC[C@H]1OC([C@@H]([C@H]1O)O)n1cnc2c1ncnc2N
InChI InChI=1S/C15H23N7O4S/c1-2-17-15(25)18-3-4-27-5-8-10(23)11(24)14(26-8)22-7-21-9-12(16)19-6-20-13(9)22/h6-8,10-11,14,23-24H,2-5H2,1H3,(H2,16,19,20)(H2,17,18,25)/t8-,10+,11-,14?/m1/s1
InChI Key CACMCLIHCDTJHL-XLAISSFRSA-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. Bezzi M, Teo SX, Muller J, Mok WC, Sahu SK, Vardy LA, Bonday ZQ, Guccione E. (2013)
Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.
Genes Dev, 27 (17): 1903-16. [PMID:24013503]
2. Meister G, Eggert C, Bühler D, Brahms H, Kambach C, Fischer U. (2001)
Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln.
Curr Biol, 11 (24): 1990-4. [PMID:11747828]
3. Smil D, Eram MS, Li F, Kennedy S, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M. (2015)
Discovery of a Dual PRMT5-PRMT7 Inhibitor.
ACS Med Chem Lett, 6 (4): 408-12. [PMID:25893041]
4. Yan F, Alinari L, Lustberg ME, Martin LK, Cordero-Nieves HM, Banasavadi-Siddegowda Y, Virk S, Barnholtz-Sloan J, Bell EH, Wojton J et al.. (2014)
Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma.
Cancer Res, 74 (6): 1752-65. [PMID:24453002]
5. Yao R, Jiang H, Ma Y, Wang L, Wang L, Du J, Hou P, Gao Y, Zhao L, Wang G et al.. (2014)
PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer.
Cancer Res, 74 (19): 5656-67. [PMID:25136067]