| Candidate ID: | R1381 |
| Source ID: | DB11590 |
| Source Type: | approved |
| Compound Type: |
small molecule
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| Compound Name: |
Thimerosal
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| Synonyms: |
[(o-carboxyphenyl)thio]ethylmercury sodium salt; BTL-TML-COVID; BTL-TML-HSV; BTL-TML001; ethyl(2-mercaptobenzoato-S)mercury sodium salt; ethylmercurithiosalicylate sodium; ethylmercurithiosalicylic acid sodium salt; mercurothiolate; o-(ethylmercurithio)benzoic acid sodium salt; sodium ethylmercurithiosalicylate; sodium merthiolate; Thimerosal; Thiomersal; Thiomersalate
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| Molecular Formula: |
C9H9HgNaO2S
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| SMILES: |
[Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O
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| Structure: |
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| DrugBank Description: |
Thiomersal (INN), commonly known in the U.S. as thimerosal, is an organomercury compound. This compound is a well-established and widely used antiseptic and antifungal agent.
Developed in 1927, thimerosal has been and is still being used as a preservative in some cosmetics, topical pharmaceuticals, and biological drug products, which includes vaccines. There has been significant concern regarding its safety and toxicity in the last several decades. Although thimerosal is banned in several countries, it continues to be included as a preservative in some vaccines in the United States and many vaccines in the developing world .
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| CAS Number: |
54-64-8
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| Molecular Weight: |
404.81
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| DrugBank Indication: |
Used as preservative in some cosmetics, topical pharmaceuticals, and biological drug products, which includes vaccines .
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| DrugBank Pharmacology: |
Thimerosal is an organomercurial compound and derivative of thiosalicyclic acid with antibacterial and antifungal properties . Thimerosal, which consists of approximately 50% mercury by weight, has been one of the most widely used preservatives in vaccines. It is metabolized/degraded to ethylmercury and thiosalicylate. Ethylmercury is an organomercurial that must be carefully distinguished from methylmercury, a closely related substance that has been the focus of many studies. Methylmercury is the type of mercury found in various species of fish . Experimental data demonstrates that the toxicokinetics of thimerosal (ethylmercury) is vastly different from that of methyl-mercury. Thus, methyl-mercury is not a suitable reference for assessing the risk from exposure to thimerosal-derived mercury .
Prior to the recent initiative to reduce or eliminate thimerosal from childhood vaccines, the maximum cumulative exposure to mercury via routine childhood vaccinations during the first 6 months of life was 187.5 micrograms. In the most recently formulated vaccines, the maximum cumulative exposure during the first 6 months of life should now be less than 3 micrograms of mercury. Currently, thimerosal may still be used in the early stages of manufacturing of certain childhood vaccines, however, only a trace remains after a chemical purification process. Note that the dose above is indicated for children 1-6 months of age is applicable only in the United States, and other countries may have varying indications .
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| DrugBank MoA: |
Although its mechanism of action is not fully understood, thimerosal inhibits sulfhydryl-containing active site of various enzymes and binds to sulfhydryl compounds, including glutathione, cysteine, and sulfhydryl groups of proteins. In addition, thimerosal activates the InsP3 calcium channel on the endoplasmic reticular membrane, thereby triggering the release of intracellular calcium resulting in a calcium-induced calcium-influx of extracellular calcium. Therefore, thimerosal may induce or inhibit various cellular functions that are dependent on the signaling of calcium .
Ethylmercury is metabolized to inorganic mercury more rapidly than methylmercury. This difference in metabolism may account for kidney pathology that can result from toxic quantities. Also, whereas the increase in oxidative stress and induction of apoptosis observed in vitro with large doses (405 μg/L to 101 mg/L) of thimerosal may explain its damaging neurological effects. The effects of low-dose ethylmercury are not completely understood to date. It is known, however, that the shorter half-life of ethylmercury (the metabolite of thimerosal) allows for very limited opportunities of ethylmercury derived from thimerosal in vaccines .
Ethylmercury is a lipophilic cation that is capable of crossing the blood-brain barrier. The octanol/water partition coefficients of methyl and ethylmercury are 1.4 to 1.8, at intracellular pH and , therefore, both organomercury compounds will primarily exist as intracellular lipophilic cations. It has been demonstrated that lipophilic cations accumulate inside mitochondria, in a Nernstian fashion, driven by the steady state membrane potential. As the typical mitochondrial membrane potential of astrocytes and neurons is between 140–170 mV, one would expect the concentration of these organomercury compounds within mitochondria to be approximately 1000 times greater than the cytosolic concentration .
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| Targets: |
Methionine synthase antagonist; Cystine/glutamate transporter antagonist; Sodium/potassium-transporting ATPase subunit gamma antagonist
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| Inclusion Criteria: |
Therapeutic strategy associated
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