| Candidate ID: | R1518 |
| Source ID: | DB14487 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Zinc acetate
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| Synonyms: |
Acetic acid, zinc salt; Dicarbomethoxyzinc; Zinc acetate anhydrous; Zinc diacetate; Zinc(II) acetate
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| Molecular Formula: |
C4H6O4Zn
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| SMILES: |
[Zn++].CC([O-])=O.CC([O-])=O
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| Structure: |
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| DrugBank Description: |
--
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| CAS Number: |
557-34-6
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| Molecular Weight: |
183.497
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| DrugBank Indication: |
Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections .
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| DrugBank Pharmacology: |
Zinc is involved in various aspects of cellular metabolism. It has been estimated that approximately 10% of human proteins may bind zinc, in addition to hundreds of proteins that transport and traffic zinc. It is required for the catalytic activity of more than 200 enzymes, and it plays a role in immune function wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is an essential element for a proper sense of taste and smell and supports normal growth and development during pregnancy, childhood, and adolescence. It is thought to have antioxidant properties, which may be protective against accelerated aging and helps to speed up the healing process after an injury; however, studies differ as to its effectiveness. Zinc ions are effective antimicrobial agents even if administered in low concentrations .
Studies on oral zinc for specific conditions shows the following evidence in various conditions :
**Colds:** Evidence suggests that if zinc lozenges or syrup are taken within 24 hours after cold symptoms start, the supplement may shorten the length of colds. The use intranasal zinc has been associated with the loss of the sense of smell, in some cases long-term or permanently .
**Wound healing:** Patients with skin ulcers and decreased levels of zinc may benefit from oral zinc supplements .
**Diahrrea**: Oral zinc supplements can reduce the symptoms of diarrhea in children with low levels of zinc, especially in cases of malnutrition .
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| DrugBank MoA: |
**Zinc has three primary biological roles**: _catalytic_, _structural_, and _regulatory_. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately 3000 human proteins including enzymes, nuclear factors, and hormones .
Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins .
In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8 .
There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine 3-5-cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to 30 September 2016 .
Zinc deficiency in humans decreases the activity of serum _thymulin_ (a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans .
The change of _Th(1)_ to _Th(2)_ function leads to cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells .
In humans, zinc deficiency may lead to the generation of new CD4+ T cells, produced in the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production .
In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers . In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In such cells, zinc was found to induce A20, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers .
The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels .
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| Targets: |
B1 bradykinin receptor; Methylated-DNA--protein-cysteine methyltransferase; Fructose-bisphosphate aldolase A; Elongation factor 1-alpha 1; Alpha-enolase; Glyceraldehyde-3-phosphate dehydrogenase, testis-specific; Nucleoside diphosphate kinase A; Protein disulfide-isomerase; Protein disulfide-isomerase A3; Peroxiredoxin-1; Phosphoserine phosphatase; Triosephosphate isomerase; Elongation factor Tu, mitochondrial; Estrogen receptor alpha; Interleukin-3; Metallothionein-2; Copper chaperone for superoxide dismutase; Histone deacetylase 1; Histone deacetylase 4; DNA-3-methyladenine glycosylase; Semenogelin-1; Superoxide dismutase [Cu-Zn]; Histone deacetylase 8; Apoptosis regulatory protein Siva; Glycine receptor subunit alpha-1; E3 ubiquitin-protein ligase Mdm2; Insulin; Utrophin; Aspartoacylase; Protein S100-A8; Protein S100-A9; Matrix metalloproteinase-9; Tumor protein p73; Protein S100-A2; Cellular tumor antigen p53; Metallothionein-3; Programmed cell death protein 6; DAN domain family member 5; Metallothionein-1A; Alpha-1B-glycoprotein; Alpha-2-macroglobulin; Angiotensinogen; Alpha-2-HS-glycoprotein; Serum amyloid P-component; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoprotein A-IV; Apolipoprotein B receptor; Apolipoprotein E; Apolipoprotein L1; Complement C1q subcomponent subunit B; Complement C1q subcomponent subunit C; Complement C1r subcomponent; Complement C1s subcomponent; Complement C3; Complement C4-B; C4b-binding protein alpha chain; C4b-binding protein beta chain; Complement C5; Lys-63-specific deubiquitinase BRCC36; Complement component C8 alpha chain; Complement component C8 beta chain; Complement component C8 gamma chain; Complement factor B; Complement factor H; Complement factor I; Clusterin; Ceruloplasmin; Carboxypeptidase N catalytic chain; Carboxypeptidase N subunit 2; Dermcidin; Desmoplakin; Coagulation factor XII; Coagulation factor XIII B chain; Prothrombin; Ficolin-3; Fibrinogen alpha chain; Fibronectin; Gelsolin; Hemoglobin subunit alpha; Hemoglobin subunit beta; Haptoglobin-related protein; Hornerin; Insulin-like growth factor-binding protein complex acid labile subunit; Ig alpha-1 chain C region; Ig mu chain C region; Immunoglobulin kappa variable 1-17; Ig kappa chain V-III region GOL; Immunoglobulin lambda variable 3-21; Inter-alpha-trypsin inhibitor heavy chain H1; Inter-alpha-trypsin inhibitor heavy chain H2; Inter-alpha-trypsin inhibitor heavy chain H3; Inter-alpha-trypsin inhibitor heavy chain H4; Immunoglobulin J chain; Junction plakoglobin; Plasma kallikrein; Kininogen-1; Keratin, type II cytoskeletal 1; Keratin, type I cytoskeletal 10; Keratin, type I cytoskeletal 14; Keratin, type I cytoskeletal 16; Keratin, type II cytoskeletal 2 epidermal; Keratin, type II cytoskeletal 5; Keratin, type II cytoskeletal 6A; Keratin, type I cytoskeletal 9; Alpha-1-acid glycoprotein 2; N-acetylmuramoyl-L-alanine amidase; Serum paraoxonase/arylesterase 1; Pregnancy zone protein; Protein S100-A7; Selenoprotein P; Alpha-1-antitrypsin; Alpha-1-antichymotrypsin; Kallistatin; Corticosteroid-binding globulin; Heparin cofactor 2; Sex hormone-binding globulin; Serotransferrin; Transthyretin; Vitronectin; Amyloid-like protein 1; Amyloid-like protein 2; Amyloid beta A4 protein; Poly [ADP-ribose] polymerase 1
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| Inclusion Criteria: |
Therapeutic strategy associated
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