NAV

Pimagedine

Identification

Generic Name
Pimagedine
DrugBank Accession Number
DB05383
Background

Pimagedine has been developed by Synvista Therapeutics, Inc for the treatment of diabetic kidney disease. It is an advanced glycation end product inhibitor which manages diabetic nephropathy, either alone or in combination with other therapies. It is beneficial in treating patients with diabetic nephropathy.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 74.0851
Monoisotopic: 74.059246212
Chemical Formula
CH6N4
Synonyms
  • Aminate base
  • Aminoguanidine
  • Guanyl hydrazine
  • Hydrazinecarboximidamide
  • Monoaminoguanidine
  • Pimagedine

Pharmacology

Indication

Investigated for use/treatment in diabetic kidney disease.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Pimagedine reportedly inhibits the formation of glycosylated proteins (advanced glycosylation end-products) and has other actions including inhibition of aldose reductase.

TargetActionsOrganism
ANitric oxide synthase, inducible
inhibitor
downregulator
Humans
UAldose reductaseNot AvailableHumans
UMetalloproteinase inhibitor 3Not AvailableHumans
AAmiloride-sensitive amine oxidase [copper-containing]
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AmantadineThe serum concentration of Amantadine can be increased when it is combined with Pimagedine.
CholineThe serum concentration of Choline can be increased when it is combined with Pimagedine.
Choline salicylateThe serum concentration of Choline salicylate can be increased when it is combined with Pimagedine.
CisplatinThe serum concentration of Cisplatin can be increased when it is combined with Pimagedine.
ClofarabineThe serum concentration of Clofarabine can be increased when it is combined with Pimagedine.
DalfampridineThe serum concentration of Dalfampridine can be increased when it is combined with Pimagedine.
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Pimagedine.
DopamineThe serum concentration of Dopamine can be increased when it is combined with Pimagedine.
EpinephrineThe serum concentration of Epinephrine can be increased when it is combined with Pimagedine.
GentamicinThe serum concentration of Gentamicin can be increased when it is combined with Pimagedine.
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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pimagedine hydrochlorideA2Z7G2RGAH1937-19-5UBDZFAGVPPMTIT-UHFFFAOYSA-N

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as guanidines. These are compounds containing a guanidine moiety, with the general structure (R1R2N)(R3R4N)C=N-R5.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Guanidines
Direct Parent
Guanidines
Alternative Parents
Hydrazones / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Aliphatic acyclic compound / Guanidine / Hydrazone / Hydrocarbon derivative / Organopnictogen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
one-carbon compound, guanidines (CHEBI:40618)
Affected organisms
Not Available

Chemical Identifiers

UNII
SCQ4EZQ113
CAS number
79-17-4
InChI Key
HAMNKKUPIHEESI-UHFFFAOYSA-N
InChI
InChI=1S/CH6N4/c2-1(3)5-4/h4H2,(H4,2,3,5)
IUPAC Name
N-aminoguanidine
SMILES
NNC(N)=N

References

General References
  1. Abdel-Rahman E, Bolton WK: Pimagedine: a novel therapy for diabetic nephropathy. Expert Opin Investig Drugs. 2002 Apr;11(4):565-74. [Article]
  2. Edelstein D, Brownlee M: Mechanistic studies of advanced glycosylation end product inhibition by aminoguanidine. Diabetes. 1992 Jan;41(1):26-9. [Article]
PubChem Compound
2146
PubChem Substance
175426990
ChemSpider
2061
BindingDB
50207159
RxNav
1311670
ChEBI
40618
ChEMBL
CHEMBL225304
ZINC
ZINC000008034829
PDBe Ligand
AGU
Wikipedia
Pimagedine
PDB Entries
2nos / 5neq / 5ny8

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceDiabetic Retinopathy (DR)1
1CompletedPreventionEndotoxaemia1
Not AvailableCompletedTreatmentAsthma1
Not AvailableCompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility8.36 mg/mLALOGPS
logP-1.8ALOGPS
logP-1.5Chemaxon
logS-0.95ALOGPS
pKa (Strongest Basic)12.01Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area87.92 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity40.84 m3·mol-1Chemaxon
Polarizability6.88 Å3Chemaxon
Number of Rings0Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9153
Blood Brain Barrier+0.8347
Caco-2 permeable-0.5826
P-glycoprotein substrateNon-substrate0.7501
P-glycoprotein inhibitor INon-inhibitor0.9597
P-glycoprotein inhibitor IINon-inhibitor0.9903
Renal organic cation transporterNon-inhibitor0.8183
CYP450 2C9 substrateNon-substrate0.8968
CYP450 2D6 substrateNon-substrate0.8024
CYP450 3A4 substrateNon-substrate0.8143
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.913
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.944
CYP450 3A4 inhibitorNon-inhibitor0.9056
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9771
Ames testNon AMES toxic0.5884
CarcinogenicityCarcinogens 0.5
BiodegradationNot ready biodegradable0.9842
Rat acute toxicity2.5602 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9236
hERG inhibition (predictor II)Non-inhibitor0.9791
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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Details1. Nitric oxide synthase, inducible
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Downregulator
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity ...
Gene Name
NOS2
Uniprot ID
P35228
Uniprot Name
Nitric oxide synthase, inducible
Molecular Weight
131116.3 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. [Article]
  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. [Article]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  5. Valente E, Assis MC, Alvim IM, Pereira GM, Plotkowski MC: Pseudomonas aeruginosa induces apoptosis in human endothelial cells. Microb Pathog. 2000 Dec;29(6):345-56. doi: 10.1006/mpat.2000.0400. [Article]
  6. Tomita M, Maeda M, Maezawa H, Usami N, Kobayashi K: Bystander cell killing in normal human fibroblasts is induced by synchrotron X-ray microbeams. Radiat Res. 2010 Mar;173(3):380-5. doi: 10.1667/RR1995.1. [Article]
  7. Draisma A, Dorresteijn MJ, Bouw MP, van der Hoeven JG, Pickkers P: The role of cytokines and inducible nitric oxide synthase in endotoxemia-induced endothelial dysfunction. J Cardiovasc Pharmacol. 2010 Jun;55(6):595-600. doi: 10.1097/FJC.0b013e3181da774b. [Article]
  8. Tassiopoulos AK, Hakim TS, Finck CM, Pedoto A, Hodell MG, Landas SK, McGraw DJ: Neutrophil sequestration in the lung following acute aortic occlusion starts during ischaemia and can be attenuated by tumour necrosis factor and nitric oxide blockade. Eur J Vasc Endovasc Surg. 1998 Jul;16(1):36-42. doi: 10.1016/s1078-5884(98)80089-0. [Article]
  9. Eslami SM, Moradi MM, Ghasemi M, Dehpour AR: Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase. J Epilepsy Res. 2016 Dec 31;6(2):51-58. doi: 10.14581/jer.16011. eCollection 2016 Dec. [Article]
  10. Zamboni DS, Rabinovitch M: Phagocytosis of apoptotic cells increases the susceptibility of macrophages to infection with Coxiella burnetii phase II through down-modulation of nitric oxide production. Infect Immun. 2004 Apr;72(4):2075-80. doi: 10.1128/IAI.72.4.2075-2080.2004. [Article]
  11. Vera Y, Erkkila K, Wang C, Nunez C, Kyttanen S, Lue Y, Dunkel L, Swerdloff RS, Sinha Hikim AP: Involvement of p38 mitogen-activated protein kinase and inducible nitric oxide synthase in apoptotic signaling of murine and human male germ cells after hormone deprivation. Mol Endocrinol. 2006 Jul;20(7):1597-609. doi: 10.1210/me.2005-0395. Epub 2006 Feb 9. [Article]
  12. Saarinen M, Ekman P, He Q, Ikeda M, Virtala M, Yu DTY, Arvilommi H, Granfors K: Elimination of Salmonella enterica serotype enteritidis in intestinal epithelial cells by mechanisms other than nitric oxide. J Med Microbiol. 2002 Jan;51(1):13-19. doi: 10.1099/0022-1317-51-1-13. [Article]
  13. Wang J, Kalhor A, Lu S, Crawford R, Ni JD, Xiao Y: iNOS expression and osteocyte apoptosis in idiopathic, non-traumatic osteonecrosis. Acta Orthop. 2015 Feb;86(1):134-41. doi: 10.3109/17453674.2014.960997. Epub 2014 Sep 5. [Article]
  14. Butterworth KT, McGarry CK, Trainor C, O'Sullivan JM, Hounsell AR, Prise KM: Out-of-field cell survival following exposure to intensity-modulated radiation fields. Int J Radiat Oncol Biol Phys. 2011 Apr 1;79(5):1516-22. doi: 10.1016/j.ijrobp.2010.11.034. Epub 2011 Jan 27. [Article]
  15. Farhad AR, Razavi F, Razavi SM, Saatchi M, Manshaei M: Histological assessment of the local effect of different concentrations of aminoguanidine hydrochloride on bone healing in rats. Dent Res J (Isfahan). 2021 Aug 18;18:63. eCollection 2021. [Article]
  16. Scalise ML, Amaral MM, Reppetti J, Damiano AE, Ibarra C, Sacerdoti F: Cytotoxic effects of Shiga toxin-2 on human extravillous trophoblast cell lines. Reproduction. 2019 Mar;157(3):297-304. doi: 10.1530/REP-18-0581. [Article]
  17. Farhad AR, Razavi SM, Nejad PA: The use of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to evaluate the role of nitric oxide on periapical healing. Dent Res J (Isfahan). 2011 Oct;8(4):197-202. doi: 10.4103/1735-3327.86038. [Article]
  18. Matsumoto H, Hayashi S, Hatashita M, Ohnishi K, Shioura H, Ohtsubo T, Kitai R, Ohnishi T, Kano E: Induction of radioresistance by a nitric oxide-mediated bystander effect. Radiat Res. 2001 Mar;155(3):387-96. doi: 10.1667/0033-7587(2001)155[0387:iorban]2.0.co;2. [Article]
  19. Deng T, Xu K, Zhang L, Zheng X: Dynamic determination of Ox-LDL-induced oxidative/nitrosative stress in single macrophage by using fluorescent probes. Cell Biol Int. 2008 Nov;32(11):1425-32. doi: 10.1016/j.cellbi.2008.08.013. Epub 2008 Aug 20. [Article]
  20. MacAllister RJ, Whitley GS, Vallance P: Effects of guanidino and uremic compounds on nitric oxide pathways. Kidney Int. 1994 Mar;45(3):737-42. doi: 10.1038/ki.1994.98. [Article]
  21. Mahattanadul S, Reanmongkol W, Yano S, Panichayupakaranant P, Phdoongsombut N, Tungsinmunkong K: Preventive and curative effects of curcumin on the development of gastric inflammatory diseases in rats. J Nat Med. 2006 Jul;60(3):191-197. doi: 10.1007/s11418-006-0035-5. Epub 2006 Apr 28. [Article]
  22. Farhad AR, Razavi SM, Rozati AR, Shekarchizade N, Manshaei M: Selective nitric oxide synthase inhibitor promotes bone healing. Dent Res J (Isfahan). 2017 Sep-Oct;14(5):306-313. doi: 10.4103/1735-3327.215965. [Article]
  23. Trainor C, Butterworth KT, McGarry CK, McMahon SJ, O'Sullivan JM, Hounsell AR, Prise KM: DNA damage responses following exposure to modulated radiation fields. PLoS One. 2012;7(8):e43326. doi: 10.1371/journal.pone.0043326. Epub 2012 Aug 17. [Article]
Details2. Aldose reductase
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Glyceraldehyde oxidoreductase activity
Specific Function
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name
AKR1B1
Uniprot ID
P15121
Uniprot Name
Aldose reductase
Molecular Weight
35853.125 Da
Details3. Metalloproteinase inhibitor 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protease binding
Specific Function
Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeli...
Gene Name
TIMP3
Uniprot ID
P35625
Uniprot Name
Metalloproteinase inhibitor 3
Molecular Weight
24144.83 Da
Details4. Amiloride-sensitive amine oxidase [copper-containing]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tum...
Gene Name
AOC1
Uniprot ID
P19801
Uniprot Name
Amiloride-sensitive amine oxidase [copper-containing]
Molecular Weight
85377.1 Da
References
  1. MARSHALL PB: Effect of sex hormones on the excretion of free histamine by male and female rats. Br J Pharmacol Chemother. 1961 Feb;16:50-8. doi: 10.1111/j.1476-5381.1961.tb00297.x. [Article]
  2. Gahl WA, Pitot HC: Reversal by aminoguanidine of the inhibition of proliferation of human fibroblasts by spermidine and spermine. Chem Biol Interact. 1978 Jul;22(1):91-8. doi: 10.1016/0009-2797(78)90152-7. [Article]
  3. IVY AC, IVY EK, KARVINEN E, LIN TM: Effect of an histaminase inhibitor (aminoguanidine) on the gastric secretory response to exogenous histamine. Am J Physiol. 1956 Aug;186(2):231-8. doi: 10.1152/ajplegacy.1956.186.2.231. [Article]

Transporters

Details1. Solute carrier family 22 member 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Kimura N, Masuda S, Katsura T, Inui K: Transport of guanidine compounds by human organic cation transporters, hOCT1 and hOCT2. Biochem Pharmacol. 2009 Apr 15;77(8):1429-36. doi: 10.1016/j.bcp.2009.01.010. Epub 2009 Jan 29. [Article]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]

Drug created at November 18, 2007 18:24 / Updated at June 28, 2022 02:24