Ammonium tetrathiomolybdate as a water-soluble and slow-release hydrogen sulfide donor

Xu, Shi; Liu, Jinbao; Meng, Fu-hui; Pacheco, Armando; Chen, Li; Xian, Ming

doi:10.1016/j.bmcl.2016.02.005

Cited by 35 publications

(33 citation statements)

References 21 publications

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“…As such, it is possible to repurpose TTM as a unique inorganic complex-based H 2 S donor, analogous to the discovery of sodium nitroprusside as a widely used nitric oxide (NO) donor ( Hottinger et al, 2014 ). To this end, we studied TTM’s H 2 S-generation and relevant activities under physiological conditions ( Xu et al, 2016 ). Using a modified methylene blue method, commercially purchased TTM (99.97% purity from Sigma-Aldrich) was used to test H 2 S release in phosphate-buffered saline under pH 5, 6, 7.4, and 8.…”

Section: Donors Of Hydrogen Sulfidementioning

confidence: 99%

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders

Liu

Chen

et al. 2017

Front. Pharmacol.

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As an important endogenous gaseous signaling molecule, hydrogen sulfide (H2S) exerts various effects in the body. A variety of pathological changes, such as cancer, glycometabolic disorders, and diabetes, are associated with altered endogenous levels of H2S, especially decreased. Therefore, the supplement of H2S is of great significance for the treatment of diseases containing the above pathological changes. At present, many efforts have been made to increase the in vivo levels of H2S by administration of gaseous H2S, simple inorganic sulfide salts, sophisticated synthetic slow-releasing controllable H2S donors or materials, and using H2S stimulating agents. In this article, we reviewed the recent development of H2S releasing/stimulating reagents and their potential applications in two common pathological processes including cancer and glycometabolic disorders.

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Section: Donors Of Hydrogen Sulfidementioning

confidence: 99%

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders

Liu

Chen

et al. 2017

Front. Pharmacol.

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“…In 2016, Xu et al (2016b) reported that ammonium tetrathiomolybdate [TTM, or (NH 4 ) 2 MoS 4 ], a compound clinically used in the treatment of copper intoxication (e.g., Wilson's disease) in patients, acts as a watersoluble H 2 S donor, which probably releases H 2 S through a simple hydrolytic process, albeit with a relatively long (hours) half-life, releases more H 2 S under acidic conditions. TTM, at concentrations of 50-200 mM, exerts protective effects against oxidantinduced cell damage in vitro (Xu et al, 2016b). TTM has many different biologic effects, including inhibition of tumor cell proliferation (Chisholm et al, 2016).…”

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confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

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“…Copper chelating can exert anticancer effects through inhibiting angiogenesis (4,6,8). However, apart from copper chelating, ATTM can release H 2 S (10,11). Studies have shown that the homeostasis of H 2 S is essential in organisms (42)(43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, our lab and others have recently discovered ATTM is a pH-dependent hydrogen sulfide (H 2 S) donor (10,11). There is no doubt that the development of ATTM as a therapeutic candidate must consider ATTM being both a copper chelator and a H 2 S releaser.…”

Section: Introductionmentioning

confidence: 99%

Is Hydrogen Sulfide a Concern During Treatment of Lung Adenocarcinoma With Ammonium Tetrathiomolybdate?

Huang

et al. 2020

Front. Oncol.

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Ammonium tetrathiomolybdate as a water-soluble and slow-release hydrogen sulfide donor

Cited by 35 publications

References 21 publications

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

Is Hydrogen Sulfide a Concern During Treatment of Lung Adenocarcinoma With Ammonium Tetrathiomolybdate?

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Ammonium tetrathiomolybdate as a water-soluble and slow-release hydrogen sulfide donor

Cited by 35 publications

References 21 publications

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

Is Hydrogen Sulfide a Concern During Treatment of Lung Adenocarcinoma With Ammonium Tetrathiomolybdate?

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International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors