pafuramidine   Click here for help

GtoPdb Ligand ID: 10842

Synonyms: DB-289 | DB289
Compound class: Synthetic organic
Comment: Pafuramidine (DB-289) is a prodrug which generates the active moiety DB-75 which exhibits antiprotozoal and antifungal activities [1]. It is a pentamidine-related dicationic molecule. Mechanistically, the drug binds to the minor groove of DNA. It has activity against parasites and also Mycobacterium tuberculosis.

pafuramidine 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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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 2
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 108.36
Molecular weight 364.15
XLogP 4.7
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 CO/N=C(/c1ccc(cc1)c1ccc(o1)c1ccc(cc1)/C(=N/OC)/N)\N
Isomeric SMILES CO/N=C(/c1ccc(cc1)c1ccc(o1)c1ccc(cc1)/C(=N/OC)/N)\N
InChI InChI=1S/C20H20N4O3/c1-25-23-19(21)15-7-3-13(4-8-15)17-11-12-18(27-17)14-5-9-16(10-6-14)20(22)24-26-2/h3-12H,1-2H3,(H2,21,23)(H2,22,24)
InChI Key UKOQVLAXCBRRGH-UHFFFAOYSA-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/)
No information available.
Summary of Clinical Use Click here for help
Pafuramidine was advanced to clinical trials but not for bacterial infections. Phase 1 trials demonstrated safety in humans.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT00803933 Trial of DB289 for the Treatment of Stage I African Trypanosomiasis Phase 2 Interventional Immtech Pharmaceuticals, Inc
NCT00302341 DB289 Versus TMP-SMX for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP) Phase 3 Interventional Immtech Pharmaceuticals, Inc This trial was put on hold by the FDA in 2007, due to safety concerns, and was subsequently terminated.
NCT00408369 Prophylactic Antimalarial Activity of DB289 in Volunteers Phase 1/Phase 2 Interventional Immtech Pharmaceuticals, Inc 2