Tag: 482.5074

Selectivity Data: Assessment, Predictions, Concordance, and Implications was written by Gao, Cen;Cahya, Suntara;Nicolaou, Christos A.;Wang, Jibo;Watson, Ian A.;Cummins, David J.;Iversen, Philip W.;Vieth, Michal. And the article was included in Journal of Medicinal Chemistry in 2013.Application of 692737-80-7 This article mentions the following:

Could high-quality in silico predictions in drug discovery eventually replace part or most of exptl. testing. To evaluate the agreement of selectivity data from different exptl. or predictive sources, we introduce the new metric concordance min. significant ratio (cMSR). Empowered by cMSR, we find the overall level of agreement between predicted and exptl. data to be comparable to that found between exptl. results from different sources. However, for mols. that are either highly selective or potent, the concordance between different exptl. sources is significantly higher than the concordance between exptl. and predicted values. We also show that computational models built from one data set are less predictive for other data sources and highlight the importance of bias correction for assessing selectivity data. Finally, we show that small-mol. target space relationships derived from different data sources and predictive models share overall similarity but can significantly differ in details. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Application of 692737-80-7).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Application of 692737-80-7

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Identification of Binding Specificity-Determining Features in Protein Families was written by Anderson, Peter C.;De Sapio, Vincent;Turner, Kevin B.;Elmer, Sidney P.;Roe, Diana C.;Schoeniger, Joseph S.. And the article was included in Journal of Medicinal Chemistry in 2012.Formula: C24H27FN6O4 This article mentions the following:

The authors present a new approach for identifying features of ligand-protein binding interfaces that predict binding selectivity and demonstrate its effectiveness for predicting kinase inhibitor specificity. The authors analyzed a large set of human kinases and kinase inhibitors using clustering of exptl. determined inhibition constants (to define specificity classes of kinases and inhibitors) and virtual ligand docking (to extract structural and chem. features of the ligand-protein binding interfaces). The authors then used statistical methods to identify features characteristic of each class. Machine learning was employed to determine which combinations of characteristic features were predictive of class membership and to predict binding specificities and affinities of new compounds Experiments showed predictions were 70% accurate. The authors’ method can automatically pinpoint on the three-dimensional binding interfaces pharmacophore-like features that act as selectivity filters. The method is not restricted to kinases, requires no prior hypotheses about specific interactions, and can be applied to any protein families for which sets of structures and ligand binding data are available. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Formula: C24H27FN6O4).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Formula: C24H27FN6O4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Screening of drugs to treat 8p11 myeloproliferative syndrome using patient- derived induced pluripotent stem cells with fusion gene CEP110-FGFR1 was written by Yamamoto, Shohei;Otsu, Makoto;Matsuzaka, Emiko;Konishi, Chieko;Takagi, Haruna;Hanada, Sachiyo;Mochizuki, Shinji;Nakauchi, Hiromitsu;Imai, Kohzoh;Tsuji, Kohichiro;Ebihara, Yasuhiro. And the article was included in PLoS One in 2015.Recommanded Product: 692737-80-7 This article mentions the following:

Induced pluripotent stem (iPS) cells provide powerful tools for studying disease mechanisms and developing therapies for diseases. The 8p11 myeloproliferative syndrome (EMS) is an aggressive chronic myeloproliferative disorder (MPD) that is caused by constitutive activation of fibroblast growth factor receptor 1. EMS is rare and, consequently, effective treatment for this disease has not been established. Here, iPS cells were generated from an EMS patient (EMS-iPS cells) to assist the development of effective therapies for EMS. When iPS cells were co-cultured with murine embryonic stromal cells, EMS-iPS cells produced more hematopoietic progenitor and hematopoietic cells, and CD34+ cells derived from EMS-iPS cells exhibited 3.2-7.2-fold more macrophage and erythroid colony forming units (CFUs) than those derived from control iPS cells. These data indicate that EMS-iPS cells have an increased hematopoietic differentiation capacity, which is characteristic of MPDs. To determine whether a tyrosine kinase inhibitor (TKI) could suppress the increased number of CFUs formed by EMS-iPS-induced CD34+ cells, cells were treated with one of four TKIs (CHIR258, PKC 412, ponatinib, and imatinib). CHIR258, PKC 412, and ponatinib reduced the number of CFUs formed by EMS-iPS-induced CD34+ cells in a dose-dependent manner, whereas imatinib did not. Similar effects were observed on primary peripheral blood cells (more than 90% of which were blasts) isolated from the patient. This study provides evidence that the EMS-iPS cell line is a useful tool for the screening of drugs to treat EMS and to investigate the mechanism underlying this disease. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Recommanded Product: 692737-80-7).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Recommanded Product: 692737-80-7

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

A Phase I Pharmacokinetic and Pharmacodynamic Study of TKI258, an Oral, Multitargeted Receptor Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors was written by Sarker, Debashis;Molife, Rhoda;Evans, T. R. Jeffrey;Hardie, Maryon;Marriott, Cheryl;Butzberger-Zimmerli, Priska;Morrison, Rosemary;Fox, Judith A.;Heise, Carla;Louie, Sharianne;Aziz, Natasha;Garzon, Felix;Michelson, Glenn;Judson, Ian R.;Jadayel, Dalal;Braendle, Edgar;de Bono, Johann S.. And the article was included in Clinical Cancer Research in 2008.Formula: C24H27FN6O4 This article mentions the following:

To determine the maximum tolerated dose (MTD) dose-limiting toxicity, and pharmacokinetic and pharmacodynamic profile of TKI258 (formerly CHIR-258). A phase I dose escalating trial in patients with advanced solid tumors was performed. Treatment was initially as single daily doses on an intermittent 7-day on/7-day off schedule. Following a protocol amendment, a second schedule comprised, during cycle 1, 7-day on/7-day off treatment followed by 14 days of continuous daily dosing; subsequent cycles comprised 28 days of daily dosing. Pharmacokinetics and evaluation of phosphorylated extracellular signal-regulated kinase (ERK) in peripheral blood mononuclear cells were done during the first 28 days of each schedule. Thirty-five patients were treated in four intermittent (25-100 mg/d) and three continuous (100-175 mg/d) dosing cohorts. Observed drug-related toxicities were nausea and vomiting, fatigue, headache, anorexia, and diarrhea. Dose-limiting toxicities were grade 3 hypertension in one patient at 100 mg continuous dosing, grade 3 anorexia in a second patient at 175 mg, and grade 3 alk. phosphatase elevation in a third patient at 175 mg. One patient had a partial response (melanoma) and two patients had stable disease >6 mo. TKI258 pharmacokinetics were linear over the dose range of 25 to 175 mg. Five of 14 evaluable patients had modulation of phosphorylated ERK levels. The MTD was defined as 125 mg/d. Evidence of antitumor activity in melanoma and gastrointestinal stromal tumors warrants further investigation, and other phase I studies are ongoing. Further pharmacodynamic evaluation is required in these studies to evaluate the biol. effects of TKI258. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Formula: C24H27FN6O4).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Formula: C24H27FN6O4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Design, Synthesis and Screening Studies of Potent Thiazol-2-Amine Derivatives as Fibroblast Growth Factor Receptor 1 Inhibitors was written by Suneel Kumar, B. V. S.;Lakshmi, Narasu;Kumar, M. Ravi;Rambabu, Gundla;Manjashetty, Thimmappa H.;Arunasree, Kalle M.;Sriram, Dharmarajan;Ramkumar, Kavya;Neamati, Nouri;Dayam, Raveendra;Sarma, J. A. R. P.. And the article was included in Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates) in 2014.Formula: C24H27FN6O4 This article mentions the following:

Fibroblast growth factor receptor 1 (FGFR1) a tyrosine kinase receptor, plays important roles in angiogenesis, embryonic development, cell proliferation, cell differentiation, and wound healing. The FGFR isoforms and their receptors (FGFRs) considered as a potential targets and under intense research to design potential anticancer agents. Fibroblast growth factors (FGF’s) and its growth factor receptors (FGFR) plays vital role in one of the critical pathway in monitoring angiogenesis. In the current study, quant. pharmacophore models were generated and validated using known FGFR1 inhibitors. The pharmacophore models were generated using a set of 28 compounds (training). The top pharmacophore model was selected and validated using a set of 126 compounds (test set) and also using external validation. The validated pharmacophore was considered as a virtual screening query to screen a database of 400,000 virtual mols. and pharmacophore model retrieved 2800 hits. The retrieved hits were subsequently filtered based on the fit value. The selected hits were subjected for docking studies to observe the binding modes of the retrieved hits and also to reduce the false positives. One of the potential hits (thiazole-2-amine derivative) was selected based the pharmacophore fit value, dock score, and synthetic feasibility. A few analogs of the thiazole-2-amine derivative were synthesized. These compounds were screened for FGFR1 activity and anti-proliferative studies. The top active compound showed 56.87% inhibition of FGFR1 activity at 50 μM and also showed good cellular activity. Further optimization of thiazole-2-amine derivatives is in progress. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Formula: C24H27FN6O4).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Formula: C24H27FN6O4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Selectivity Data: Assessment, Predictions, Concordance, and Implications was written by Gao, Cen;Cahya, Suntara;Nicolaou, Christos A.;Wang, Jibo;Watson, Ian A.;Cummins, David J.;Iversen, Philip W.;Vieth, Michal. And the article was included in Journal of Medicinal Chemistry in 2013.Application of 692737-80-7 This article mentions the following:

Could high-quality in silico predictions in drug discovery eventually replace part or most of exptl. testing. To evaluate the agreement of selectivity data from different exptl. or predictive sources, we introduce the new metric concordance min. significant ratio (cMSR). Empowered by cMSR, we find the overall level of agreement between predicted and exptl. data to be comparable to that found between exptl. results from different sources. However, for mols. that are either highly selective or potent, the concordance between different exptl. sources is significantly higher than the concordance between exptl. and predicted values. We also show that computational models built from one data set are less predictive for other data sources and highlight the importance of bias correction for assessing selectivity data. Finally, we show that small-mol. target space relationships derived from different data sources and predictive models share overall similarity but can significantly differ in details. In the experiment, the researchers used many compounds, for example, 4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7Application of 692737-80-7).

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate (cas: 692737-80-7) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Application of 692737-80-7

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics