Antioxidant with free radical scavenging activity; cytoprotective effects on gastrointestinal mucosa (mechanism not fully quantified) [1]
Inhibitor of hepatic stellate cell (HSC) activation and hepatocellular carcinoma proliferation (mechanism not fully quantified) [2]

Polaprezinc (8-16 μg/ml) significantly inhibited proliferation of LX-2 hepatic stellate cells after 3 days (vs. 0 μg/ml: Day 3, P=0.0025; Day 4, P<0.0001). No dose-dependent effect was observed between 8 and 16 μg/ml. [2]

In hepG2 and huh7 hepatocellular carcinoma cells, Polaprezinc (8-16 μg/ml) reduced proliferation after 5 days (hepG2: Day 5, P=0.0033; Day 6, P<0.0001). Colony formation assays confirmed dose-dependent inhibition (hepG2: 16 μg/ml, P<0.0001; huh7: 16 μg/ml, P<0.0001). [2]

Transwell migration assays showed Polaprezinc (8 μg/ml) reduced LX-2 cell migration by ~50% (P=0.0082), indicating suppression of HSC motility. [2]

RT-qPCR analysis revealed Polaprezinc (8 μg/ml) downregulated fibrotic markers in LX-2 cells: Collagen I (P<0.0001), fibronectin (P=0.0008), and α-SMA (P=0.0004). [2]

A chelate molecule consisting of zinc ions, L-carnosine, β-alanine dipeptide, and L-histidine, Polaprezinc (PZ) is an anti-ulcer medication. Polaprezinc scavenges free radicals and has antioxidant properties. In animal models, polaprezinc has been demonstrated to be efficacious against acute radiation proctitis and to have anti-inflammatory properties following radiation exposure [1].

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In C57BL/6J mice receiving 15 Gy total body irradiation (TBI), oral pretreatment with Polaprezinc (100 mg/kg) 2 hours prior to radiation significantly increased viable crypt counts vs. post-treatment or untreated controls: Duodenum – 39.8 vs. 20.2 (P=0.04); Ileum – 66.1 vs. 43 (P=0.02). Pre-irradiation administration showed superior radioprotection. [1]

After 2 Gy TBI, Polaprezinc pretreatment reduced apoptosis in intestinal crypts at 8 hours (peak apoptosis time): Apoptotic index decreased by 61% in duodenum (0.022 vs. 0.056), 58% in jejunum (0.044 vs. 0.106, P=0.01), and 38% in ileum (0.052 vs. 0.084). [1]

Radiation-induced apoptosis predominantly occurred at positions 1-10 from crypt base (stem cell zone). Polaprezinc reduced apoptotic cells at these critical positions across duodenum, jejunum, and ileum (Fig. 5). [1]

Cell proliferation assay: LX-2, hepG2, or huh7 cells seeded in 96-well plates (1×10³/well) with RPMI 1640 + 10% FBS. Treated with 0/8/16 μg/ml Polaprezinc. MTS reagent added daily, incubated 4 h at 37°C. Absorbance measured at 490 nm for 6 consecutive days. [2]

Colony formation assay: 500 cells/well seeded in 24-well plates. After 14-day incubation, cells fixed with methanol, stained with 0.1% crystal violet. Colonies (>300 cells) counted under inverted microscope. [2]

Migration assay: 5×10⁴ LX-2 cells in serum-free medium added to Transwell upper chamber. Lower chamber contained RPMI 1640 + 15% FBS. After 24 h incubation, migrated cells fixed/stained with crystal violet and counted. [2]

RT-qPCR: LX-2 cells treated with 0/8 μg/ml Polaprezinc for 7 days. RNA extracted, reverse-transcribed to cDNA. Collagen I, fibronectin, α-SMA expression analyzed via SYBR Green PCR using GAPDH normalization. Cycling: 95°C 10 min → 40 cycles (95°C 15 sec → 60°C 30 sec → 72°C 30 sec). [2]

Crypt survival assay: Mice received oral Polaprezinc (100 mg/kg in drinking water) 2 hours before or after 15 Gy TBI. Tissues (duodenum, jejunum, ileum) harvested 3 days post-irradiation, fixed, H&E-stained, and viable crypts (≥10 cells/cross-section) counted. [1]

Apoptosis kinetics assay: Polaprezinc administered 2 hours before 2 Gy TBI. Duodenum, jejunum, ileum, and rectum harvested at 0, 4, and 8 hours post-IR. Apoptotic cells identified by H&E-stained fragments; apoptotic index and cell position recorded. [1]

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

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Metabolism / Metabolites
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%.

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

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

[1]. Polaprezinc protects normal intestinal epithelium against exposure to ionizing radiation in mice. Mol Clin Oncol. 2016 Oct;5(4):377-381.

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. It was determined that polaprezinc may be effective in pressure ulcer treatment. A study in 2013 showed that CO-administration of polaprezinc may be effective against small intestine mucosal injury associated with long-term aspirin therapy.
Polaprezinc is an orally bioavailable chelate composed of zinc and L-carnosine, with potential gastroprotective, anti-oxidant, anti-ulcer and anti-inflammatory activities. Upon administration, polaprezinc increases the expression of various anti-oxidant enzymes, such as 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) in the gastric mucosa, which protect cells against reactive oxygen species (ROS). In addition, this agent inhibits the activity of the transcription factor nuclear factor-kappaB (NF-kappaB) and reduces the expression of several pro-inflammatory cytokines, such as interleukin (IL) 1beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-a). Polaprezinc also increases the expression of various growth factors, such as platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), and various heat shock proteins (HSPs), including HSP90, HSP70, HSP60, HSP47, HSP27, and HSP10. This protects against damages to, and accelerates healing of the gastric mucosa.

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Drug Indication
Peptic ulcer disease, dyspepsia.

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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.

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Polaprezinc is an anti-ulcer drug with documented antioxidant and free radical scavenging properties. It protects intestinal epithelium from radiation damage by suppressing apoptosis, particularly in crypt stem cell zones. [1]

Mechanism may involve inhibition of p53/p21/Bax pathways (cited from prior studies) and reduction of oxidative stress. Pre-irradiation timing (2 hours) is critical for efficacy, aligning with gastrointestinal transit time in mice. [1]

Primary application: Prevention of radiation-induced gastrointestinal toxicity during abdominal/pelvic radiotherapy. Clinical studies suggest no interference with tumor response to radiation. [1]

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Polaprezinc reverses liver fibrosis by deactivating HSCs: Suppresses proliferation/migration and downregulates ECM markers (collagen I, fibronectin, α-SMA). Gene ontology analysis in hepG2 cells treated with 16 μg/ml Polaprezinc revealed altered expression of 202 genes (>1.5-fold) involved in cytoskeleton organization, cell motility, and proliferation regulation. [2]

Proposed mechanism: Targets HSC activation and disrupts tumor microenvironment. Clinical relevance: Potential novel therapy for HCC patients with concurrent cirrhosis. [2]

C9H12N4O3ZN

289.6

288.02

C, 37.33; H, 4.18; N, 19.35; O, 16.57; Zn, 22.58

107667-60-7

51051629

White to off-white solid powder

557.6ºC at 760 mmHg

300ºC

291ºC

3

6

4

17

265

1

O=C1[C@@H]([N-](C2=O)[Zn+2](NCC2)[O-]1)CC3=CN=CN3

GFWBKUDRXMQSFD-FJXQXJEOSA-M

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);/p-1/t7-;/m0./s1

3-aminopropanoyl-[(1S)-1-carboxy-2-(1H-imidazol-5-yl)ethyl]azanide;zinc

Z 103; Polaprezinc; 107667-60-7; Zinc L-carnosine; DTXSID7048615; beta-alanyl-L-histidinato zinc; NCGC00181764-01; CHEMBL3184454; DTXCID4028541; Polaprezinc

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~3.37 mg/mL (~11.68 mM)
DMSO :< 1 mg/mL

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)