2-Arylidene Hydrazinecarbodithioates as Potent, Selective Inhibitors of Cystathionine γ-Lyase (CSE)

Bhattacharjee, Abir; Sinha, Antara; Ratia, Kiira; Yin, Liang; Delgado-Rivera, Loruhama; Petukhov, Pavel A.; Thatcher, Gregory R. J.; Wardrop, Duncan J.

doi:10.1021/acsmedchemlett.7b00313

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…Intuitively, a higher Z ′ factor (a larger difference between the signals obtained for positive and negative controls and/or smaller standard deviations in their signals) is expected to result in a higher hit rate, although this is also dependent on the statistical cutoff used to determine a hit . In order to confirm whether this expected correlation existed, the confirmed % hit rate for campaigns identified in Table , ,,,,,− Table , ,,,,,− ,,,,,,,− ,,, and several additional papers − was plotted as a function of Z ′ factor (Figure ).…”

Section: Other Factors Influencing Hit Identification In Screening Ca...mentioning

confidence: 98%

“…The identified campaigns − (Table ) had 75 examples of hit to lead development. In many cases few details of the screening library are available, so for the purposes of this study lead development from a fragment was considered to have occurred where the initial hit had a molecular weight of 300 Da or less (a typical upper molecular weight limit used in fragment screening campaigns).…”

Section: What Makes a “Successful” Screening Campaign?mentioning

confidence: 99%

“…In order to investigate this, data were assembled from studies reported in Table , ,,,,,− Table , ,,,,,− ,,,,,,,− ,,,, and several additional papers − as noted above. Confirmed % hit rates were plotted as a function of library size (Figure ).…”

Section: Other Factors Influencing Hit Identification In Screening Ca...mentioning

confidence: 99%

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High-Throughput Screening for the Discovery of Enzyme Inhibitors

Lloyd

2020

J. Med. Chem.

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Enzymes are common targets in high-throughput screening and related campaigns. An analysis of papers published between 1990 and 2018 showed that kinases were the most common enzymes investigated, fluorescence-based assays were the most common readout method, and cancer and bacterial infections were the most common therapeutic areas. High-throughput screening and fragment-screening campaigns published between 2017 and 2019 were analyzed in more depth, giving 75 examples of hit to lead development. Kinases, phosphatases, proteases, and peptidases were the most common targets, fluorescent assays were the most commonly used, and a wide variety of structural features were observed within the derived drugs. Hit frequency was largely independent of library size and positively correlated with Z′ value for the assay. Binding of metal ions to library compounds and substrates is an underappreciated source of false-positive results and unreproducible behavior.

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Section: Other Factors Influencing Hit Identification In Screening Ca...mentioning

confidence: 98%

Section: What Makes a “Successful” Screening Campaign?mentioning

confidence: 99%

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High-Throughput Screening for the Discovery of Enzyme Inhibitors

Lloyd

2020

J. Med. Chem.

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“…As the result, AOAA suppresses H 2 S production through all enzymatic and non-enzymatic pathways. There are several additional molecules that selectively inhibit activities of CBS [ 160 , 161 , 162 , 163 , 164 ] or CTH [ 165 , 166 , 167 , 168 , 169 ] to exert anticancer effect. On the other hand, there was no selective inhibitor for 3-MST until recently, Hanaoka, K. et al (2017) established a high-throughput screening (HTS) method to screen 174,118 compounds and several potential inhibitors for 3-MST were identified.…”

Section: Hydrogen Sulfide Based Therapeuticsmentioning

confidence: 99%

The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

Wang

Chu

Lin

2021

IJMS

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Hydrogen Sulfide (H2S), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of H2S-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived H2S plays various roles during cancer development reveals opportunities to target H2S-mediated signaling pathways in cancer therapy. In this review, we will focus on the mechanism of H2S-mediated protein persulfidation and the detailed information about the dysregulation of H2S-producing enzymes and metabolism in different cancer types. We will also provide an update on mechanisms of H2S-mediated cancer progression and summarize current options to modulate H2S production for cancer therapy.

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“…Another compound 2-arylidene hydrazinecarbodithioates ( Fig. 5) was revealed to be more active than the benchmark inhibitors, and notably, it had higher selectivity for CSE compared to CBS (94). S-3-carboxpropyl-L-cysteine (CPC) (Fig.…”

Section: Effect Of Cse Inhibition In Breast Cancermentioning

confidence: 99%

Therapeutic potential of endogenous hydrogen sulfide inhibition in breast cancer (Review)

Liu

Deng

et al. 2021

Oncol Rep

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Hydrogen sulfide (H 2 S), the third gas signal molecule, is associated with the modulation of various physiological and pathological processes. Recent studies have reevealed that endogenous H 2 S may promote proliferation, induce angiogenesis and inhibit apoptosis, thereby stimulating oncogenesis. Conversely, decreased endogenous H 2 S release suppresses growth of various tumors including breast cancer. This observation suggests an alternative tumor therapy strategy by inhibiting H 2 S-producing enzymes to reduce the release of endogenous H 2 S. Breast cancer is the most common type of cancer in women. Due to the lack of approved targeted therapy, its recurrence and metastasis still affect its clinical treatment. In recent years, significant progress has been made in the control of breast cancer by using inhibitors on H 2 S-producing enzymes. This review summarized the roles of endogenous H 2 S-producing enzymes in breast cancer and the effects of the enzyme inhibitors on anticancer and anti-metastasis, with the aim of providing new insights for the treatment of breast cancer.

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2-Arylidene Hydrazinecarbodithioates as Potent, Selective Inhibitors of Cystathionine γ-Lyase (CSE)

Cited by 11 publications

References 30 publications

High-Throughput Screening for the Discovery of Enzyme Inhibitors

High-Throughput Screening for the Discovery of Enzyme Inhibitors

The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

Therapeutic potential of endogenous hydrogen sulfide inhibition in breast cancer (Review)

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