Identification

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Name
Polaprezinc
Accession Number
DB09221
Type
Small Molecule
Groups
Experimental
Description

Polaprezinc is a chelated form of zinc and L-carnosine. It is a zinc-related medicine approved for the first time in Japan, which has been clinically used to treat gastric ulcers 5. It was determined that polaprezinc may be effective in pressure ulcer treatment 3. A study in 2013 showed that CO-administration of polaprezinc may be effective against small intestine mucosal injury associated with long-term aspirin therapy 1.

Structure
Thumb
Synonyms
  • beta-alanyl-l-histidinato zinc
  • Zinc L-carnosine
External IDs
Z 103 / Z-103
International/Other Brands
HAPPI-XT / POLAPREZINC 15% / POLAPREZINC OD SAWAI / POLAZEPRINC CHOSEIDO / POLAZEPRINC DAIKO SEIYAKU / POLAZEPRINC MYLAN / POLAZEPRINC NISSHIN SEIYAKU / Promac (Zeria Pharmaceuticals Co.) / PROMAC 15% / PROMAC-D
Categories
UNII
0WA1B15A1Z
CAS number
107667-60-7
Weight
Average: 289.6
Monoisotopic: 288.020082
Chemical Formula
C9H12N4O3Zn
InChI Key
IGXZLYMCFZHNKW-FJXQXJEOSA-L
InChI
InChI=1S/C9H14N4O3.Zn/c10-2-1-8(14)13-7(9(15)16)3-6-4-11-5-12-6;/h4-5,7H,1-3,10H2,(H3,11,12,13,14,15,16);/q;+2/p-2/t7-;/m0./s1
IUPAC Name
zinc(2+) ion (2S)-2-[(3-aminopropanoyl)azanidyl]-3-(1H-imidazol-5-yl)propanoate
SMILES
[Zn++].[H][C@@](CC1=CN=CN1)([N-]C(=O)CCN)C([O-])=O

Pharmacology

Indication

Peptic ulcer disease, dyspepsia 6.

Pharmacodynamics

Used to treat/manage peptic ulcer disease or irritation of the gastrointestinal tract by promoting tissue healing by the elimination of free radicals 1.

Mechanism of action

Polaprezinc increases the expression of various antioxidant enzymes, including superoxide dismutase 1 (SOD-1), SOD-2, heme oxygenase-1 (HO-1), glutathione S-transferase (GST), glutathione peroxidase (GSH-px), peroxidredoxin-1 (PRDX1; PRXI) and PRXD5 (PRXV).

This process occurs in the gastric mucosa, defending mucosal cells against reactive oxygen species. This drug inhibits the activity of the transcription factor nuclear factor-kappaB (NF-kB) and decreases the expression of various inflammatory cytokines, including interleukin (IL) 1beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-a).

Polaprezinc also promotes the expression of numerous growth factors, including as platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), in addition to various heat shock proteins (HSPs), including HSP90, HSP70, HSP60, HSP47, HSP27, and HSP10. This process promotes tissue growth and protects against damage the gastric mucosa 6.

TargetActionsOrganism
UTumor necrosis factor
inhibitor
Humans
UInterleukin-6
inhibitor
Humans
UInterleukin-3
inhibitor
Humans
UVascular endothelial growth factor receptor 1
agonist
Humans
UBeta-nerve growth factor
agonist
Humans
UPlatelet-derived growth factor receptor beta
agonist
Humans
UHeat shock protein HSP 90-alpha
agonist
Humans
UHeat shock protein HSP 90-beta
agonist
Humans
Absorption

Intestinal absorption of L-CAZ was studied in rats by Sano et al. 7 using 14C- and 65Zn-labeled compounds. They suggested that L-CAZ dissociates to its components, L-carnosine and zinc, during intestinal absorption 7.

Volume of distribution
Not Available
Protein binding

It has been observed that a diet heavy in proteins accelerates the absorption of zinc 7, implying that amino acids with low molecular weight may carry zinc into the circulatory system via complexation.

Metabolism

Excretion rates of polaprezinc after a single administration using 14C-labeled drug to rats are 4.1% in urine, 13.3% in feces, and 38.8% in exhalation, and those using 65Zn-labeled L-CAZ are 0.3% in urine and 85.0% in feces. The absorption rate of zinc is estimated to be about 11% 7.

Route of elimination

Intestinal absorption of the drug was examined using 14C- and 65Zn-labeled compounds. Polaprezinc metabolizes into its components, L-carnosine and zinc, during intestinal absorption. It was found that the excretion rates after one administration using 14C-labeled L-CAZ to rats were 4.1% in urine, 13.3% in feces, and 38.8% in exhalation. The study using 65Zn-labeled Paleprozinc were 0.3% in urine and 85.0% in the feces. The absorption rate of zinc is estimated to be approximately 11% 7.

Half life

The half-life of polaprezinc has been studied in rats and found to be approximately 2 hours 8.

Clearance
Not Available
Toxicity

Copper deficiency can occur because polaprezinc contains zinc, which inhibits copper absorption. Pancytopenia and anemia, associated with copper deficiency, have been noted in patients with malnutrition 9. Precautions should be taken to monitor for symptoms of pancytopenia and anemia, especially in patients with poor nutrition. The toxic effects of high polaprezinc dosage were studied in dogs. In the studies, dosages of 50 mg/kg/day and higher resulted in vomiting, diarrhea and hypersalivation, reduced appetite and reduction in body weight gain for females administered high doses. In addition, increased alkaline phosphatase (marker of hepatic damage) and decreased urinary specific gravity (suggestive of renal damage), and pathological tissue changes in the kidney of the high dosed dogs of both genders were noted. These changes resolved upon completing a period of drug withdrawal 4.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Bamet-UD2Polaprezinc can cause a decrease in the absorption of Bamet-UD2 resulting in a reduced serum concentration and potentially a decrease in efficacy.
CarbamazepinePolaprezinc can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy.
CeftibutenPolaprezinc can cause a decrease in the absorption of Ceftibuten resulting in a reduced serum concentration and potentially a decrease in efficacy.
CephalexinPolaprezinc can cause a decrease in the absorption of Cephalexin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Chenodeoxycholic acidPolaprezinc can cause a decrease in the absorption of Chenodeoxycholic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Cholic AcidPolaprezinc can cause a decrease in the absorption of Cholic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
CinoxacinPolaprezinc can cause a decrease in the absorption of Cinoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
CiprofloxacinPolaprezinc can cause a decrease in the absorption of Ciprofloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
ClomocyclinePolaprezinc can cause a decrease in the absorption of Clomocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
DeferasiroxPolaprezinc can cause a decrease in the absorption of Deferasirox resulting in a reduced serum concentration and potentially a decrease in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Watari I, Oka S, Tanaka S, Aoyama T, Imagawa H, Shishido T, Yoshida S, Chayama K: Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study. BMC Gastroenterol. 2013 Jul 4;13:108. doi: 10.1186/1471-230X-13-108. [PubMed:23826914]
  2. Takei M: [Development of polaprezinc research]. Yakugaku Zasshi. 2012;132(3):271-7. [PubMed:22382829]
  3. Sakae K, Yanagisawa H: Oral treatment of pressure ulcers with polaprezinc (zinc L-carnosine complex): 8-week open-label trial. Biol Trace Elem Res. 2014 Jun;158(3):280-8. doi: 10.1007/s12011-014-9943-5. Epub 2014 Apr 3. [PubMed:24691900]
  4. Matsuda K, Yamaguchi I, Wada H: Toxicity of the novel anti-peptic ulcer agent polaprezinc in beagle dogs. Arzneimittelforschung. 1995 Jan;45(1):52-60. [PubMed:7893270]
  5. Promac [Link]
  6. NCI dictionary [Link]
  7. Applicability of Zinc Complex of L-Carnosine for Medical Use [Link]
  8. Residence Time of Polaprezinc (Zinc L-Carnosine Complex) in the Rat Stomach and Adhesiveness to Ulcerous Sites [Link]
  9. Revision of Precautions for Poplaprezinc [Link]
External Links
KEGG Drug
D01611
PubChem Compound
6918055
PubChem Substance
310265128
ChemSpider
7993200
ChEBI
32024
ChEMBL
CHEMBL3184454
Wikipedia
Zinc_L-carnosine
MSDS
Download (49.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedTreatmentEarly Gastric Cancer / Gastric Adenoma / Gastric Adenoma and Early Gastric Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)300https://www.trc-canada.com/product-detail/?P688000
Predicted Properties
PropertyValueSource
Water Solubility10.9 mg/mLALOGPS
logP-0.64ALOGPS
logP-4.5ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)3.37ChemAxon
pKa (Strongest Basic)9.13ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area121.13 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity65.6 m3·mol-1ChemAxon
Polarizability21.52 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Hybrid peptides
Direct Parent
Hybrid peptides
Alternative Parents
Histidine and derivatives / N-acyl-L-alpha-amino acids / Beta amino acids and derivatives / Heteroaromatic compounds / Imidazoles / Amino acids / Secondary carboxylic acid amides / Carboxylic acid salts / Organic transition metal salts / Carboxylic acids
show 8 more
Substituents
Hybrid peptide / Histidine or derivatives / N-acyl-l-alpha-amino acid / N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / Beta amino acid or derivatives / Alpha-amino acid or derivatives / Azole / Heteroaromatic compound / Imidazole
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Interleukin-6 receptor binding
Specific Function
Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Inv...
Gene Name
IL6
Uniprot ID
P05231
Uniprot Name
Interleukin-6
Molecular Weight
23717.965 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Interleukin-3 receptor binding
Specific Function
Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blo...
Gene Name
IL3
Uniprot ID
P08700
Uniprot Name
Interleukin-3
Molecular Weight
17232.905 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Receptor signaling protein activity
Specific Function
Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signal...
Gene Name
NGF
Uniprot ID
P01138
Uniprot Name
Beta-nerve growth factor
Molecular Weight
26958.53 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Tpr domain binding
Specific Function
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Under...
Gene Name
HSP90AA1
Uniprot ID
P07900
Uniprot Name
Heat shock protein HSP 90-alpha
Molecular Weight
84659.015 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Utp binding
Specific Function
Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Under...
Gene Name
HSP90AB1
Uniprot ID
P08238
Uniprot Name
Heat shock protein HSP 90-beta
Molecular Weight
83263.475 Da
References
  1. NCI dictionary [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Zinc ion binding
Specific Function
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Gene Name
SOD1
Uniprot ID
P00441
Uniprot Name
Superoxide dismutase [Cu-Zn]
Molecular Weight
15935.685 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Signal transducer activity
Specific Function
Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the a...
Gene Name
HMOX1
Uniprot ID
P09601
Uniprot Name
Heme oxygenase 1
Molecular Weight
32818.345 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Superoxide dismutase activity
Specific Function
Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Gene Name
SOD2
Uniprot ID
P04179
Uniprot Name
Superoxide dismutase [Mn], mitochondrial
Molecular Weight
24721.955 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Glutathione transferase activity
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chlorid...
Gene Name
GSTT1
Uniprot ID
P30711
Uniprot Name
Glutathione S-transferase theta-1
Molecular Weight
27334.755 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Sh3 domain binding
Specific Function
Protects the hemoglobin in erythrocytes from oxidative breakdown.
Gene Name
GPX1
Uniprot ID
P07203
Uniprot Name
Glutathione peroxidase 1
Molecular Weight
22087.94 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Thioredoxin peroxidase activity
Specific Function
Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system but not from glutaredoxin. May play an important role in eliminating pe...
Gene Name
PRDX1
Uniprot ID
Q06830
Uniprot Name
Peroxiredoxin-1
Molecular Weight
22110.19 Da
References
  1. NCI dictionary [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Rna polymerase iii regulatory region dna binding
Specific Function
Reduces hydrogen peroxide and alkyl hydroperoxides with reducing equivalents provided through the thioredoxin system. Involved in intracellular redox signaling.
Gene Name
PRDX5
Uniprot ID
P30044
Uniprot Name
Peroxiredoxin-5, mitochondrial
Molecular Weight
22086.245 Da
References
  1. NCI dictionary [Link]

Drug created on October 21, 2015 18:49 / Updated on June 04, 2019 07:09