Identification
- Generic Name
- Polaprezinc
- DrugBank Accession Number
- DB09221
- Background
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 5,6. 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.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Polaprezinc (DB09221)
- Weight
- Average: 289.6
Monoisotopic: 288.020082 - Chemical Formula
- C9H12N4O3Zn
- Synonyms
- beta-Alanyl-L-histidinato zinc
- Polaprezinc
- Zinc L-carnosine
- External IDs
- Z 103
- Z-103
Pharmacology
- Indication
Peptic ulcer disease, dyspepsia 6.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism UTumor necrosis factor inhibitorHumans UInterleukin-6 inhibitorHumans UInterleukin-3 inhibitorHumans UVascular endothelial growth factor receptor 1 agonistHumans UBeta-nerve growth factor agonistHumans UPlatelet-derived growth factor receptor beta agonistHumans UHeat shock protein HSP 90-alpha agonistHumans UHeat shock protein HSP 90-beta agonistHumans - 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
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareCarbamazepine Polaprezinc can cause a decrease in the absorption of Carbamazepine resulting in a reduced serum concentration and potentially a decrease in efficacy. Ceftibuten Polaprezinc can cause a decrease in the absorption of Ceftibuten resulting in a reduced serum concentration and potentially a decrease in efficacy. Cephalexin Polaprezinc can cause a decrease in the absorption of Cephalexin resulting in a reduced serum concentration and potentially a decrease in efficacy. Cinoxacin Polaprezinc can cause a decrease in the absorption of Cinoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy. Ciprofloxacin Polaprezinc can cause a decrease in the absorption of Ciprofloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Promac (Zeria Pharmaceuticals Co.) / Promac-D
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Azole / Beta amino acid or derivatives / Carbonyl group / Carboxamide group show 25 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 0WA1B15A1Z
- CAS number
- 107667-60-7
- 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
- (4S)-3-(3-aminopropanoyl)-4-[(1H-imidazol-5-yl)methyl]-1-oxa-3-aza-2-zincacyclopentan-5-one
- SMILES
- NCCC(=O)N1[Zn]OC(=O)[C@@H]1CC1=CN=CN1
References
- General References
- 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. [Article]
- Takei M: [Development of polaprezinc research]. Yakugaku Zasshi. 2012;132(3):271-7. [Article]
- 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. [Article]
- 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. [Article]
- Promac [Link]
- NCI dictionary [Link]
- Applicability of Zinc Complex of L-Carnosine for Medical Use [Link]
- Residence Time of Polaprezinc (Zinc L-Carnosine Complex) in the Rat Stomach and Adhesiveness to Ulcerous Sites [Link]
- Revision of Precautions for Poplaprezinc [Link]
- External Links
- KEGG Drug
- D01611
- PubChem Compound
- 6918055
- PubChem Substance
- 310265128
- ChemSpider
- 7993200
- 2179843
- ChEBI
- 32024
- ChEMBL
- CHEMBL3184454
- Wikipedia
- Zinc_L-carnosine
- MSDS
- Download (49.5 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Unknown Status Treatment Pain / Periodontal Index 1 1, 2 Completed Treatment Castration Resistant Prostate Cancer 1 Not Available Completed Treatment Early Gastric Cancer / Gastric Adenoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 300 https://www.trc-canada.com/product-detail/?P688000 - Predicted Properties
Property Value Source Water Solubility 41.1 mg/mL ALOGPS logP -1.2 ALOGPS logP -2.8 Chemaxon logS -0.85 ALOGPS pKa (Strongest Acidic) 12.92 Chemaxon pKa (Strongest Basic) 9.13 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 101.31 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 53.83 m3·mol-1 Chemaxon Polarizability 23.29 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-000f-0090000000-472a70ff841a6a9344e5 - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 155.6541571 predictedDarkChem Lite v0.1.0 [M+H]+ 157.3163571 predictedDarkChem Lite v0.1.0
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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Choi HS, Lim JY, Chun HJ, Lee M, Kim ES, Keum B, Seo YS, Jeen YT, Um SH, Lee HS, Kim CD, Ryu HS, Sul D: The effect of polaprezinc on gastric mucosal protection in rats with ethanol-induced gastric mucosal damage: comparison study with rebamipide. Life Sci. 2013 Jul 30;93(2-3):69-77. doi: 10.1016/j.lfs.2013.05.019. Epub 2013 Jun 3. [Article]
- NCI dictionary [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- 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
- Choi HS, Lim JY, Chun HJ, Lee M, Kim ES, Keum B, Seo YS, Jeen YT, Um SH, Lee HS, Kim CD, Ryu HS, Sul D: The effect of polaprezinc on gastric mucosal protection in rats with ethanol-induced gastric mucosal damage: comparison study with rebamipide. Life Sci. 2013 Jul 30;93(2-3):69-77. doi: 10.1016/j.lfs.2013.05.019. Epub 2013 Jun 3. [Article]
- NCI dictionary [Link]
Drug created at October 22, 2015 00:49 / Updated at February 03, 2022 21:01