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Record Information
Version2.0
Creation Date2009-07-30 17:59:04 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3526
Identification
Common NamePentamidine
ClassSmall Molecule
DescriptionPentamidine is only found in individuals that have used or taken this drug. It is an antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of pneumocystis pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [PubChem] The mode of action of pentamidine is not fully understood. It is thought that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids, and proteins.
Compound Type
  • Amide
  • Amine
  • Antifungal Agent
  • Antiprotozoal Agent
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Trypanocidal Agent
Chemical Structure
Thumb
Synonyms
Synonym
1,3-Bis(4-amidinophenoxy)pentane
1,5-Bis(4-amidinophenoxy)pentane
4, 4'-Diamidinodiphenoxypentane
4,4'-(1,5-Pentanediylbis(oxy))bis-benzenecarboximidamide
4,4'-(Pentamethylenedioxy)dibenzamidine
4,4'-Diamidinodiphenoxypentane
NebuPent
P,P'-(pentamethylenedioxy)dibenzamidine
Pentacarinat
Pentacrinat
Pentam
Pentam 300
Pentamide
Pentamidin
Pentamidina
Pentamidindiisetionat
Pentamidine Isethionate
Pentamidinum
Pneumopent
PNT
Chemical FormulaC19H24N4O2
Average Molecular Mass340.420 g/mol
Monoisotopic Mass340.190 g/mol
CAS Registry Number100-33-4
IUPAC Name4-{[5-(4-carbamimidoylphenoxy)pentyl]oxy}benzene-1-carboximidamide
Traditional Namepentamidine
SMILESNC(=N)C1=CC=C(OCCCCCOC2=CC=C(C=C2)C(N)=N)C=C1
InChI IdentifierInChI=1S/C19H24N4O2/c20-18(21)14-4-8-16(9-5-14)24-12-2-1-3-13-25-17-10-6-15(7-11-17)19(22)23/h4-11H,1-3,12-13H2,(H3,20,21)(H3,22,23)
InChI KeyInChIKey=XDRYMKDFEDOLFX-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenol ethers
Sub ClassNot Available
Direct ParentPhenol ethers
Alternative Parents
Substituents
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • Monocyclic benzene moiety
  • Carboximidamide
  • Ether
  • Carboxylic acid amidine
  • Amidine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point186.0°C (decomposes)
Boiling PointNot Available
SolubilityComplete
LogP4
Predicted Properties
PropertyValueSource
Water Solubility0.024 g/LALOGPS
logP1.32ALOGPS
logP2.32ChemAxon
logS-4.2ALOGPS
pKa (Strongest Basic)12.13ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area118.2 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity120.53 m³·mol⁻¹ChemAxon
Polarizability38.85 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4u-0902000000-3844069e5553bbf605a6JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0006-0009000000-e30f537a55b02f867429JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0006-0009000000-18ffa88d8e83e0c224b3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0309000000-22a206e2fffa6ce5cf2fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00dr-0900000000-d135e9c44dbf5da10735JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0900000000-d01e29cdf614c3660180JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0006-0009000000-1499530d0d768e480fd7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0006-0009000000-3c60569ced478a95001fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-0209000000-58a168dde59140860009JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00dr-0901000000-7cd36861b140e4e5a6a2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00di-0900000000-60dfcd75868e869bcbf7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-00di-0009000000-6677c6c06aa266d05ff1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-00dr-0900000000-210e86ac8fe8716be765JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-00di-0900000000-d01e29cdf614c3660180JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0006-0009000000-e30f537a55b02f867429JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0006-0009000000-18ffa88d8e83e0c224b3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-00dr-0900000000-d135e9c44dbf5da10735JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00di-0309000000-22a206e2fffa6ce5cf2fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-00di-0900000000-a005235fbf0235ec242aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00di-0309000000-ba9999e56127535cc0beJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0119000000-03540964e2e9de4c6fdeJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-059f-1889000000-e8ee9afdfbafe4df23edJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-059i-4900000000-44f0a38ad73ee56728eaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0409000000-15c819a9688c0d5dd79fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0904000000-cc51d663fb7c9ccf5339JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000i-4900000000-1a2483dd0fa6cb115ce5JSpectraViewer
Toxicity Profile
Route of ExposureAbsorbed poorly through the gastrointestinal tract and is usually administered parenterally.
Mechanism of ToxicityThe mode of action of pentamidine is not fully understood. It is thought that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids, and proteins.
MetabolismHepatic. Half Life: 9.1-13.2 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of pneumonia due to Pneumocystis carinii.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include pain, nausea, anorexia, hypotension, fever, rash, bad taste in mouth, confusion/hallucinations, dizziness, and diarrhea.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00738
HMDB IDHMDB14876
PubChem Compound ID4735
ChEMBL IDCHEMBL55
ChemSpider ID4573
KEGG IDC07420
UniProt IDNot Available
OMIM ID
ChEBI ID45081
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPentamidine
PDB IDPNT
ACToR IDNot Available
Wikipedia LinkPentamidine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Nguewa PA, Fuertes MA, Cepeda V, Iborra S, Carrion J, Valladares B, Alonso C, Perez JM: Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin. Chem Biodivers. 2005 Oct;2(10):1387-400. [17191940 ]
  2. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Shankar SM, Nania JJ: Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy. Paediatr Drugs. 2007;9(5):301-9. [17927302 ]
General Function:
Zinc ion binding
Specific Function:
Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.
Gene Name:
S100B
Uniprot ID:
P04271
Molecular Weight:
10712.985 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 50015245
Dissociation1 uMNot AvailableBindingDB 50015245
References
  1. Markowitz J, Chen I, Gitti R, Baldisseri DM, Pan Y, Udan R, Carrier F, MacKerell AD Jr, Weber DJ: Identification and characterization of small molecule inhibitors of the calcium-dependent S100B-p53 tumor suppressor interaction. J Med Chem. 2004 Oct 7;47(21):5085-93. [15456252 ]
  2. Yoshimura C, Miyafusa T, Tsumoto K: Identification of small-molecule inhibitors of the human S100B-p53 interaction and evaluation of their activity in human melanoma cells. Bioorg Med Chem. 2013 Mar 1;21(5):1109-15. doi: 10.1016/j.bmc.2012.12.042. Epub 2013 Jan 8. [23375094 ]
General Function:
Peptidyl-cysteine s-nitrosylase activity
Specific Function:
Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.
Gene Name:
GAPDH
Uniprot ID:
P04406
Molecular Weight:
36053.0 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>50 uMNot AvailableBindingDB 50015245
References
  1. Bressi JC, Verlinde CL, Aronov AM, Shaw ML, Shin SS, Nguyen LN, Suresh S, Buckner FS, Van Voorhis WC, Kuntz ID, Hol WG, Gelb MH: Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of Trypanosomatidae via structure-based drug design. J Med Chem. 2001 Jun 21;44(13):2080-93. [11405646 ]
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502.7 uMNot AvailableBindingDB 50015245
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Drug transmembrane transporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A2
Uniprot ID:
Q86VL8
Molecular Weight:
65083.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5010.4 uMNot AvailableBindingDB 50015245
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5022.1 uMNot AvailableBindingDB 50015245
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.2 uMNot AvailableBindingDB 50015245
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Toxin transporter activity
Specific Function:
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name:
SLC22A3
Uniprot ID:
O75751
Molecular Weight:
61279.485 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC509.5 uMNot AvailableBindingDB 50015245
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Serine-type peptidase activity
Specific Function:
Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing.
Gene Name:
ST14
Uniprot ID:
Q9Y5Y6
Molecular Weight:
94769.01 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.16 uMNot AvailableBindingDB 50015245
References
  1. Enyedy IJ, Lee SL, Kuo AH, Dickson RB, Lin CY, Wang S: Structure-based approach for the discovery of bis-benzamidines as novel inhibitors of matriptase. J Med Chem. 2001 Apr 26;44(9):1349-55. [11311057 ]
General Function:
Trna methyltransferase activity
Specific Function:
Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp).
Gene Name:
TRDMT1
Uniprot ID:
O14717
Molecular Weight:
44596.17 Da
References
  1. Sun T, Zhang Y: Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation. Nucleic Acids Res. 2008 Mar;36(5):1654-64. doi: 10.1093/nar/gkm1180. Epub 2008 Feb 7. [18263620 ]
General Function:
Protein tyrosine/serine/threonine phosphatase activity
Specific Function:
Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II.
Gene Name:
PTP4A3
Uniprot ID:
O75365
Molecular Weight:
19534.69 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5053.6 uMNot AvailableBindingDB 50015245