Identification

Name
Pimagedine
Accession Number
DB05383  (EXPT00459, DB02533)
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
  • Aminoguanidine
  • Hydrazinecarboximidamide
Product Ingredients
IngredientUNIICASInChI Key
Pimagedine hydrochlorideA2Z7G2RGAH1937-19-5UBDZFAGVPPMTIT-UHFFFAOYSA-N
Categories
Not Available
UNII
SCQ4EZQ113
CAS number
79-17-4
Weight
Average: 74.0851
Monoisotopic: 74.059246212
Chemical Formula
CH6N4
InChI Key
HAMNKKUPIHEESI-UHFFFAOYSA-N
InChI
InChI=1S/CH6N4/c2-1(3)5-4/h4H2,(H4,2,3,5)
IUPAC Name
1-aminoguanidine
SMILES
NNC(N)=N

Pharmacology

Indication

Investigated for use/treatment in diabetic kidney disease.

Structured Indications
Not Available
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
UNitric oxide synthase, inducible
inhibitor
Human
UAldose reductaseNot AvailableHuman
UMetalloproteinase inhibitor 3Not AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

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. [PubMed:11922864]
  2. Edelstein D, Brownlee M: Mechanistic studies of advanced glycosylation end product inhibition by aminoguanidine. Diabetes. 1992 Jan;41(1):26-9. [PubMed:1727735]
External Links
PubChem Compound
2146
PubChem Substance
175426990
ChemSpider
2061
BindingDB
50207159
ChEBI
40618
ChEMBL
CHEMBL225304
HET
AGU
PDB Entries
2nos / 5neq / 5ny8

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionEndotoxaemia1
1RecruitingBasic ScienceRetinopathy, Diabetic1

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

Taxonomy

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
Guanidine / Hydrazone / Organopnictogen compound / Hydrocarbon derivative / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
one-carbon compound, guanidines (CHEBI:40618)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. [PubMed: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. [PubMed:17016423]
  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. [PubMed:10592235]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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

Transporters

Kind
Protein
Organism
Human
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. [PubMed:19426682]
  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. [PubMed:10592235]

Drug created on November 18, 2007 11:24 / Updated on December 01, 2017 17:37