Tag: M.W=500-550

Liu, Wen-Wen published the artcileFemtomole-Scale High-Throughput Screening of Protein Ligands with Droplet-Based Thermal Shift Assay, SDS of cas: 863127-77-9, the publication is Analytical Chemistry (Washington, DC, United States) (2017), 89(12), 6678-6685, database is CAplus and MEDLINE.

There is a great demand to measure protein-ligand interactions in rapid and low cost way. Here the authors developed a microfluidic droplet-based thermal shift assay (dTSA) system for high throughput screening of small-mol. protein ligands. The system is composed of a nanoliter droplet array chip, a microfluidic droplet robot, and a real-time fluorescence detection system. Total 324 assays could be performed in parallel in a single chip with an 18 × 18 droplet array. The consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole scale), which is significantly reduced by over 3 orders of magnitude compared with those in 96 or 384-well plate-based systems. The authors also observed the implementation of TSA in nanoliter droplet format could substantially improve assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which can be ascribed to the enhanced thermal conduction in small volume reactors. The dTSA system was optimized by studying the effect of droplet volumes, as well as protein and fluorescent dye (SYPRO Orange) concentrations To demonstrate its potential in drug discovery, the authors applied the dTSA system in screening inhibitors of human thrombin with a com. library containing 100 different small mol. compounds, and two inhibitors were successfully identified and confirmed.

Analytical Chemistry (Washington, DC, United States) published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, SDS of cas: 863127-77-9.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Sodeifian, Gholamhossein published the artcileSolubility of Dasatinib monohydrate (anticancer drug) in supercritical CO₂: Experimental and thermodynamic modeling, Application of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, the publication is Journal of Molecular Liquids (2022), 117899, database is CAplus.

Solubility of Dasatinib monohydrate (DAS, an anticancer drug) in supercritical carbon dioxide (Sc-CO₂) was examined statically at temperatures ranging from 308 to 338 K and pressures ranging from 120 to 270 bar. Based on the results, mole fractions of DAS dissolved in the Sc-CO₂ were reported as 0.45 x 10^-6 to 9.08 x 10^-6, leading to solubilities in the range of 0.004-0.082 g/L, resp. The exptl. data were correlated using three types of models: (1) 20 existing empirical and semi-empirical models including 3-6 parameters on the basis of functional dependencies, (2) temperature-dependent and temperature-independent variants of the Peng-Robinson’s (PR) cubic equation of state with a conventional mixing rule, and (3) solid-liquid equilibrium models. All tested models could produce appropriate fits to the solubility data at acceptable levels of accuracy, although solid-liquid equilibrium models led to the superiority based on AARD and AICc criterion. Furthermore, solvation and sublimation enthalpies were estimated

Journal of Molecular Liquids published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C12H14IN, Application of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Fujimoto, Shota published the artcileIndocyanine green-labeled dasatinib as a new fluorescent probe for molecular imaging of gastrointestinal stromal tumors, SDS of cas: 863127-77-9, the publication is Journal of Gastroenterology and Hepatology (2021), 36(5), 1253-1262, database is CAplus and MEDLINE.

It is difficult to differentiate gastrointestinal stromal tumors (GISTs) from other subepithelial lesions under gastrointestinal endoscopy. Because most GISTs express tyrosine kinase receptor c-KIT, fluorescence-labeled c-KIT-specific tyrosine kinase inhibitors seem to be useful agents for mol. imaging of GIST. We aimed to develop a near-IR fluorescent imaging technol. for GIST targeting c-KIT using the novel fluorescent probe indocyanine green-labeled dasatinib (ICG-dasatinib) and to investigate the antitumor effect of ICG-dasatinib on GIST cells. Indocyanine green-labeled dasatinib was synthesized by labeling linker-induced dasatinib with ICG derivative 3-indocyanine-green-acyl-1,3-thiazolidine-2-thione. Human GIST cell lines GIST-T1 and GIST-882M were incubated with ICG-dasatinib and observed by fluorescent microscopy. GIST cells were incubated with ICG-dasatinib, unlabeled dasatinib, or imatinib, and cell viabilities were evaluated. S.c. GIST model mice or orthotopic GIST model rats were i.v. injected with ICG-dasatinib and observed using an IVIS Spectrum. Strong fluorescent signals of ICG-dasatinib were observed in both GIST cell lines in vitro. IC₅₀ values for ICG-dasatinib, unlabeled dasatinib, and imatinib were 13.9, 1.17, and 16.2 nM in GIST-T1 and 26.6, 3.63, and 47.6 nM in GIST-882M cells, resp. ICG-dasatinib accumulated in s.c. xenografts in mice. Fluorescent signals were also observed in liver and gallbladder, indicating biliary excretion; however, fluorescence intensity of tumors was significantly higher than that of intestine after washing. Strong fluorescent signals were observed in orthotopic xenografts through the covering normal mucosa in rats. Indocyanine green-labeled dasatinib could visualize GIST cells and xenografted tumors. The antitumor effect of ICG-dasatinib was preserved to the same degree as imatinib.

Journal of Gastroenterology and Hepatology published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, SDS of cas: 863127-77-9.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Roy, Saikat published the artcileStructural and Physicochemical Aspects of Dasatinib Hydrate and Anhydrate Phases, Safety of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, the publication is Crystal Growth & Design (2012), 12(4), 2122-2126, database is CAplus and MEDLINE.

Crystal structures for the com. monohydrate form and an anhydrate form of dasatinib, an oral anticancer agent, are presented along with characterization by Raman spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric anal. Solubility measurements conducted in water reveal that the anhydrate has dramatically improved solubility compared to the com. hydrate form. Finally, dasatinib is a rare example of a promiscuous solvate former, and the basis for this behavior can now be understood by examining the poor packing efficiency in the unsolvated form.

Crystal Growth & Design published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, Safety of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Reddy, B. Rasmitha published the artcileFormulation and evaluation of dasatinib immediate release tablets, Related Products of piperazines, the publication is World Journal of Pharmacy and Pharmaceutical Sciences (2014), 3(3), 1113-1123, database is CAplus.

Dasatinib is a selective Tyrosine Kinase Inhibitor (TKI) used in treatment of chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Dasatinib have become first line drug in the pharmacotherapy of patients with CML. This is because the drug possesses tolerability and safety advantages over the other Tyrosine Kinase Inhibitors. Tablets of Dasatinib were prepared using different superdisintegrants (Sodium Starch Glycolate, Croscarmellose, and Crospovidone) by wet granulation method. Nine formulations (F1-F9) of immediate release oral tablets were prepared by using different disintegrants to get desired release profile. The drug-excipients interaction was investigated by FTIR. The granules and tablets of Dasatinib evaluated for various pre and post compression parameters like Angle of repose Compressibility index, Hausner’s ratio, Tablet hardness, Friability, Weight variation, Drug content and in vitro dissolution Their results were found satisfactory. DSC studies have shown that drug is stable in the formulation. It is concluded that in vitro dissolution studies show the release is in the following order of superdisintegrants: Croscarmellose > Sodium Starch Glycolate > Crospovidone. Maximum in vitro dissolution was found to be with Formulation F-2 and it clearly shows due to Croscarmellose (7.9%).

World Journal of Pharmacy and Pharmaceutical Sciences published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, Related Products of piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Zhang, Jun published the artcileCytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes, Safety of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, the publication is Toxicology Letters (2018), 138-148, database is CAplus and MEDLINE.

Of the 34 FDA approved oral small-mol. kinase inhibitors (KI), 23 (68%) have warnings for hepatotoxicity in product labeling. To better understand the mechanisms of KI hepatotoxicity and whether such effects can be predicted, the authors examined 34 KIs for cytotoxicity in primary rat and human hepatocytes. The hepatocytes were treated with KIs at ten concentrations normalized to maximal therapeutic blood levels (Cmax). At 5 and 24 h post treatment, lactate dehydrogenase or alanine amtransferase leakage, caspase 3/7 activities and cellular ATP levels were measured. At 1 to 100-fold Cmax, while 5 KIs were neither toxic to human nor rat hepatocytes, 3 KIs showed similar cytotoxicity in both species and 26 KIs showed species-biased cytotoxicity, with 16 KIs being more toxic to human hepatocytes and 10 KIs being more toxic to rat hepatocytes. At concentrations of 1-, 2.5-, 5-, 10-, 100-fold Cmax, the number of cytotoxic KIs in human hepatocytes was 4, 8, 11, 14 and 27, resp., and the corresponding number in rat hepatocytes was 1, 4, 9, 12 and 27, resp. When hepatocyte cytotoxicity at 100-fold Cmax was used to predict KI clin. hepatotoxicity reflected in product labeling, the accuracy was 0.65 with human hepatocytes and 0.59 with rat cells. When the criterion of daily dose ≥100 mg or Cmax ≥1.1 μM was used to predict KI hepatotoxicity, the accuracy was 0.56 or 0.47, resp. These results suggest both indirect and direct drug-induced hepatocyte toxicity may contribute to the mechanisms of KI-induced hepatotoxicity seen clin. and use of primary hepatocytes is a useful in vitro model to help predict such toxicity.

Toxicology Letters published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C7H5BClNO2, Safety of N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Hamamoto, Tomoyuki published the artcileVisualization and analysis of adverse reactions of molecularly targeted anticancer agents using the self-organizing map (SOM), Product Details of C22H28ClN7O3S, the publication is Yakugaku Zasshi (2014), 134(10), 1069-1080, database is CAplus and MEDLINE.

Molecularly targeted anticancer agents cause a variety of adverse reactions compared with conventional anticancer agents because of their unique mechanisms of action. Sources of drug information such as package inserts (PIs) provide primarily document-based and numerical information. Therefore it is not easy to obtain a complete picture of drugs with similar effects, or to understand differences among drugs. In this study we used the self-organizing map (SOM) technique to visualize the adverse reactions indicated on PIs of 23 molecularly targeted anticancer agents as of March 2013. In both the presence/absence version and the frequency version, SOM was divided into domains according to mechanism of action, antibody drug or low-mol. weight drug, and mol. target. The component planes of the 753 adverse reaction items in the frequency version enabled us to grasp all available information and differences among the drugs. In some component planes in the presence/absence version, an adverse reaction that had not been reported for a drug but had already been reported for its proximally positioned drug (s) as of March 2013, was found to be reported thereafter by the Drug Safety Update (DSU) or the Adverse Event Report Search System “CzeekV,” which is based on FDA Adverse Event Reporting System (FAERS). Our results suggest that visualization of the adverse reactions of molecularly targeted anticancer agents by the SOM technique is useful not only to acquire all available information and differences among drugs, but also to predict the appearance of adverse reactions.

Yakugaku Zasshi published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, Product Details of C22H28ClN7O3S.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics