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Polaprezinc

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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
Similar Structures
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
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Pharmacology

Indication

Peptic ulcer disease, dyspepsia 6.

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Contraindications & Blackbox Warnings
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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

Adverse Effects
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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.

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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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.
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.
Food Interactions
Not Available

Products

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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
  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. [Article]
  2. Takei M: [Development of polaprezinc research]. Yakugaku Zasshi. 2012;132(3):271-7. [Article]
  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. [Article]
  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. [Article]
  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]
KEGG Drug
D01611
PubChem Compound
6918055
PubChem Substance
310265128
ChemSpider
7993200
RxNav
2179843
ChEBI
32024
ChEMBL
CHEMBL3184454
Wikipedia
Zinc_L-carnosine
MSDS
Download (49.5 KB)

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
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3Unknown StatusTreatmentPain / Periodontal Indexes1somestatusstop reasonjust information to hide
1, 2CompletedTreatmentCastration Resistant Prostate Cancer1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentEarly Gastric Cancer / Gastric Adenoma1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
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 Solubility41.1 mg/mLALOGPS
logP-1.2ALOGPS
logP-2.8Chemaxon
logS-0.85ALOGPS
pKa (Strongest Acidic)12.92Chemaxon
pKa (Strongest Basic)9.13Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area101.31 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity53.83 m3·mol-1Chemaxon
Polarizability23.29 Å3Chemaxon
Number of Rings2Chemaxon
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-MSsplash10-000f-0090000000-472a70ff841a6a9344e5
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-155.6541571
predicted
DarkChem Lite v0.1.0
[M+H]+157.3163571
predicted
DarkChem Lite v0.1.0

Targets

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insights and accelerate drug research.
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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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Details1. Tumor necrosis factor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General 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 action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity)
Specific Function
Cytokine activity
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
Details2. Interleukin-6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable)
Specific Function
Cytokine activity
Gene Name
IL6
Uniprot ID
P05231
Uniprot Name
Interleukin-6
Molecular Weight
23717.965 Da
Details3. Interleukin-3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells (PubMed:2556442). Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated (PubMed:10779277, PubMed:32889153). In addition, plays an important role in neural cell proliferation and survival (PubMed:23226269). Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation (PubMed:12816992). Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB (PubMed:29374162). Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program (By similarity). Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK (PubMed:27862234)
Specific Function
Cytokine activity
Gene Name
IL3
Uniprot ID
P08700
Uniprot Name
Interleukin-3
Molecular Weight
17232.905 Da
Details4. Vascular endothelial growth factor receptor 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General 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 survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275)
Specific Function
Atp binding
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. NCI dictionary [Link]
Details5. Beta-nerve growth factor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:14976160, PubMed:20978020). Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (Probable) (PubMed:20978020). The immature NGF precursor (proNGF) functions as a ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse. In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (By similarity). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI (PubMed:20164177). Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer. The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (By similarity)
Specific Function
Growth factor activity
Gene Name
NGF
Uniprot ID
P01138
Uniprot Name
Beta-nerve growth factor
Molecular Weight
26958.53 Da
References
  1. NCI dictionary [Link]
Details6. Platelet-derived growth factor receptor beta
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Tyrosine-protein kinase that acts as a 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 development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor
Specific Function
Atp binding
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. NCI dictionary [Link]
Details7. Heat shock protein HSP 90-alpha
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General 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. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812)
Specific Function
Atp binding
Gene Name
HSP90AA1
Uniprot ID
P07900
Uniprot Name
Heat shock protein HSP 90-alpha
Molecular Weight
84659.015 Da
References
  1. NCI dictionary [Link]
Details8. Heat shock protein HSP 90-beta
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General 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. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059)
Specific Function
Atp binding
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

Details1. Superoxide dismutase [Cu-Zn]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Destroys radicals which are normally produced within the cells and which are toxic to biological systems
Specific Function
Copper ion binding
Gene Name
SOD1
Uniprot ID
P00441
Uniprot Name
Superoxide dismutase [Cu-Zn]
Molecular Weight
15935.685 Da
References
  1. NCI dictionary [Link]
Details2. Heme oxygenase 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron (PubMed:11121422, PubMed:19556236, PubMed:7703255). Affords protection against programmed cell death and this cytoprotective effect relies on its ability to catabolize free heme and prevent it from sensitizing cells to undergo apoptosis (PubMed:20055707)
Specific Function
Enzyme binding
Gene Name
HMOX1
Uniprot ID
P09601
Uniprot Name
Heme oxygenase 1
Molecular Weight
32818.345 Da
References
  1. NCI dictionary [Link]
Details3. Superoxide dismutase [Mn], mitochondrial
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems
Specific Function
Dna binding
Gene Name
SOD2
Uniprot ID
P04179
Uniprot Name
Superoxide dismutase [Mn], mitochondrial
Molecular Weight
24750.015 Da
References
  1. NCI dictionary [Link]
Details4. Glutathione S-transferase theta-1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General 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 chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide
Specific Function
Glutathione peroxidase activity
Gene Name
GSTT1
Uniprot ID
P30711
Uniprot Name
Glutathione S-transferase theta-1
Molecular Weight
27334.755 Da
References
  1. NCI dictionary [Link]
Details5. Glutathione peroxidase 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide, as well as several fatty acid-derived hydroperoxides (PubMed:11115402, PubMed:36608588). In platelets catalyzes the reduction of 12-hydroperoxyeicosatetraenoic acid, the primary product of the arachidonate 12-lipoxygenase pathway (PubMed:11115402)
Specific Function
Glutathione peroxidase activity
Gene Name
GPX1
Uniprot ID
P07203
Uniprot Name
Glutathione peroxidase 1
Molecular Weight
22087.94 Da
References
  1. NCI dictionary [Link]
Details6. Peroxiredoxin-1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (PubMed:9497357). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By similarity)
Specific Function
Cadherin binding
Gene Name
PRDX1
Uniprot ID
Q06830
Uniprot Name
Peroxiredoxin-1
Molecular Weight
22110.19 Da
References
  1. 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]
  2. NCI dictionary [Link]
Details7. Peroxiredoxin-5, mitochondrial
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events
Specific Function
Antioxidant activity
Gene Name
PRDX5
Uniprot ID
P30044
Uniprot Name
Peroxiredoxin-5, mitochondrial
Molecular Weight
22086.245 Da
References
  1. 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]
  2. NCI dictionary [Link]

Drug created at October 22, 2015 00:49 / Updated at February 03, 2022 21:01