Development of a matrix-assisted laser desorption/ionization–mass spectrometry screening test to evidence reversible and irreversible inhibitors of CDC25 phosphatases

Synthesis and Molecular modeling of some new chalcones derived from coumarine as CDC25 phosphatases inhibitors

“…In case of inhibition, the applied procedure is also able to inform about its reversibility or irreversibility. 28 Compounds with the highest values in biological analysis as inhibitor (3, 4 and 5) gave a positive results in MALDI-TOFMS Their protonated molecular ion directly appeared in the mass spectrum meaning that they behaves as reversible inhibitors as described by Sibille et al 29 and Bana et al 17 . …”

Screening of indeno[1,2-b]indoloquinones by MALDI-MS: a new set of potential CDC25 phosphatase inhibitors brought to light

“…The screening of CDC25 inhibitors was already described by Sibille et al 16 . The first step consisted in the incubation at 37 C of CDC25A or -C with the evaluated compound at a final concentration of 2 Â 10 À3 M. CDC25 phosphatases were solubilized in Tris A buffer (50 mM Tris, 50 mM NaCl, 1 mM ethylenediaminetetraacetic acid [EDTA], and 1 mM dithiothreitol [DTT], pH 8.0) at a concentration of approximately 2 Â 10 À5 M for isoform A and 2.2 Â 10 À5 M for isoform C. Then, 30 mL of CDC25A or 50 mL of CDC25C was incubated with 10 mL of the evaluated compound for 1 h. The next step was a ultracentrifugation of the incubate for 8 min at 12 000 rpm using a Microcon Õ centrifugal filter unit (Millipore, Cork, Irland) with a mass cutoff of 30 kDa (Millipore).…”

“…Evidencing new potential inhibitors by the mean of biological tests is expensive and time-consuming. In 2012, inspired by studies carried out by Hannewald et al on tubulin 14 and DHFR 15 , Sibille et al 16 proposed a rapid approach for screening CDC25 inhibitors using MALDI mass spectrometry. Based on the target-ligand interactions in which CDC25s are the target, this method allows highlighting the most promising candidates from a set of molecules.…”

“…Based on the target-ligand interactions in which CDC25s are the target, this method allows highlighting the most promising candidates from a set of molecules. However, Sibille et al 16 completed the screening procedure with an additional step able to answer the question about the reversibility of the inhibition. Nevertheless, complementary biological tests, for instance cytotoxicity and IC 50 , have to be carried out obviously but only for the most interesting candidates.…”

Synthesis and Biological Activities of Novel 2,5-Disubstituted- 1,3,4-thiadiazole Derivatives

“…在 PTPs 的家族中, Cdc25s 是细胞分裂周期的关键调节剂 [19] . 在 哺乳类动物, 已经确定有三个 Cdc25 亚型, 分别为 Cdc25A, Cdc25B 和 Cdc25C [21] . Cdc25A 和 Cdc25B 在许 多人类癌症(如乳腺癌、结肠癌、子宫颈癌、肺癌等)中 都是过度表达的, 因此, Cdc25A/Cdc25B 已成为治疗癌 症的重要药物靶标 [19,22] .…”