pralatrexate   Click here for help

GtoPdb Ligand ID: 6840

Synonyms: Folotyn® | PDX
Approved drug
pralatrexate is an approved drug (FDA (2009))
Compound class: Synthetic organic
Comment: Inhibits dihydrofolate reductase, GAR transformylase and thymidylate synthase. The INN document specifies that pralatrexate is a racemic mixture of two epimers. These epimers are represented by the PubChem entries CID 23230419 and CID 11155808. We do not specify stereochemistry at the carbon atom which determines the two epimers, therefore our image represents the mixture.

SARS-CoV-2 and COVID-19: Pralatrexate has been identified as an inhibitor of the viral RNA-dependent RNA polymerase (RdRp; nsp12) from SARS-CoV-2 [2]. This translates to inhibition of SARS-CoV-2 replication in vitro (EC50 8 nM). Structural anaylsis suggests that the interaction points between pralatrexate and RdRp are distinct from those between remdesivir and RdRp.
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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

pralatrexate is commercially available from our sponsors

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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Click here for structure editor
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 12
Hydrogen bond donors 5
Rotatable bonds 11
Topological polar surface area 207.3
Molecular weight 477.18
XLogP -2.16
No. Lipinski's rules broken 1

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 C#CCC(c1ccc(cc1)C(=O)NC(C(=O)O)CCC(=O)O)Cc1cnc2c(n1)c(N)nc(n2)N
Isomeric SMILES C#CCC(c1ccc(cc1)C(=O)N[C@H](C(=O)O)CCC(=O)O)Cc1cnc2c(n1)c(N)nc(n2)N
InChI InChI=1S/C23H23N7O5/c1-2-3-14(10-15-11-26-20-18(27-15)19(24)29-23(25)30-20)12-4-6-13(7-5-12)21(33)28-16(22(34)35)8-9-17(31)32/h1,4-7,11,14,16H,3,8-10H2,(H,28,33)(H,31,32)(H,34,35)(H4,24,25,26,29,30)/t14?,16-/m0/s1
InChI Key OGSBUKJUDHAQEA-WMCAAGNKSA-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. Izbicka E, Diaz A, Streeper R, Wick M, Campos D, Steffen R, Saunders M. (2009)
Distinct mechanistic activity profile of pralatrexate in comparison to other antifolates in in vitro and in vivo models of human cancers.
Cancer Chemother Pharmacol, 64 (5): 993-9. [PMID:19221750]
2. Zhang H, Yang Y, Li J, Wang M, Saravanan KM, Wei J, Tze-Yang Ng J, Tofazzal Hossain M, Liu M, Zhang H et al.. (2020)
A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro.
PLoS Comput Biol, 16 (12): e1008489. [PMID:33382685]