Category: 6055-19-2

Kirkland, David; Aardema, Marilyn; Henderson, Leigh; Mueller, Lutz published the artcile< Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens. I. Sensitivity, specificity and relative predictivity>, Electric Literature of 6055-19-2, the main research area is genotoxicity in vitro assay carcinogen noncarcinogen discrimination.

The performance of a battery of three of the most commonly used in vitro genotoxicity tests, i.e., Ames + mouse lymphoma assay (MLA) + in vitro micronucleus (MN) or chromosomal aberrations (CA) test, was evaluated for its ability to discriminate rodent carcinogens and non-carcinogens, from a large database of over 700 chems. compiled from the CPDB (“”Gold””), NTP, IARC and other publications. We re-evaluated many (113 MLA and 30 CA) previously published genotoxicity results in order to categories the performance of these assays using the response categories we established. The sensitivity of the three-test battery was high. Of the 553 carcinogens for which there were valid genotoxicity data, 93% of the rodent carcinogens evaluated in at least one assay gave pos. results in at least one of the three tests. Combinations of two and three test systems had greater sensitivity than individual tests resulting in sensitivities of around 90% or more, depending on test combination. Only 19 carcinogens (out of 206 tested in all three tests, considering CA and MN as alternatives) gave consistently neg. results in a full three-test battery. Most were either carcinogenic via a non-genotoxic mechanism (liver enzyme inducers, peroxisome proliferators, hormonal carcinogens) considered not necessarily relevant for humans, or were extremely weak (presumed) genotoxic carcinogens (e.g. N-nitrosodiphenylamine). Two carcinogens (5-chloro-o-toluidine, 1,1,2,2-tetrachloroethane) may have a genotoxic element to their carcinogenicity and may have been expected to produce pos. results somewhere in the battery. We identified 183 chems. that were non-carcinogenic after testing in both male and female rats and mice. There were genotoxicity data on 177 of these. The specificity of the Ames test was reasonable (73.9%), but all mammalian cell tests had very low specificity (i.e. below 45%), and this declined to extremely low levels in combinations of two and three test systems. When all three tests were performed, 75-95% of non-carcinogens gave pos. (i.e. false pos.) results in at least one test in the battery. The extremely low specificity highlights the importance of understanding the mechanism by which genotoxicity may be induced (whether it is relevant for the whole animal or human) and using weight of evidence approaches to assess the carcinogenic risk from a pos. genotoxicity signal. It also highlights deficiencies in the current prediction from and understanding of such in vitro results for the in vivo situation. It may even signal the need for either a reassessment of the conditions and criteria for pos. results (cytotoxicity, solubility, etc.) or the development and use of a completely new set of in vitro tests (e.g. mutation in transgenic cell lines, systems with inherent metabolic activity avoiding the use of S9, measurement of genetic changes in more cancer-relevant genes or hotspots of genes, etc.). It was very difficult to assess the performance of the in vitro MN test, particularly in combination with other assays, because the published database for this assay is relatively small at this time. The specificity values for the in vitro MN assay may improve if data from a larger proportion of the known non-carcinogens becomes available, and a larger published database of results with the MN assay is urgently needed if this test is to be appreciated for regulatory use. However, specificity levels of <50% will still be unacceptable. Despite these issues, by adopting a relative predictivity (RP) measure (ratio of real:false results), it was possible to establish that pos. results in all three tests indicate the chem. is greater than three times more likely to be a rodent carcinogen than a non-carcinogen. Likewise, neg. results in all three tests indicate the chem. is greater than two times more likely to be a rodent non-carcinogen than a carcinogen. This RP measure is considered a useful tool for industry to assess the likelihood of a chem. possessing carcinogenic potential from batteries of pos. or neg. results. Mutation Research, Genetic Toxicology and Environmental Mutagenesis published new progress about Aflatoxins Role: ADV (Adverse Effect, Including Toxicity), BIOL (Biological Study) (crude). 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Electric Literature of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Laine, Ensio; Tuominen, Virpi; Jalonen, Hannu; Kahela, Paavo published the artcile< Effect of storage conditions on structure of cyclophosphamide>, Formula: C7H17Cl2N2O3P, the main research area is cyclophosphamide stability storage; dehydration cyclophosphamide monohydrate.

The effect of aging on the structure of cyclophosphamide (I) [50-18-0] was studied under different storage conditions. I hydrate [6055-19-2] is preserved as such if the relation humidity is >70% and the temperature is <30°, otherwise the monohydrate form will change to an anhydrous form. The monohydrate-anhydrous transition was reversible. Acta Pharmaceutica Fennica published new progress about Dehydration process. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Formula: C7H17Cl2N2O3P.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Pasula, Chandra Sekhar; Tadakaluru, Yasodha Lakshmi; Sannidhi, Ranga Suresh; Pujari, Venkata Suresh Reddy; Chirumamilla, Venkata Satish Kumar; Reddy, Y. Raja Ratna published the artcile< Comparative analysis of cyclophosphamide monohydrate cytotoxicity in healthy human lymphocytes and L5178Y TK+/- mouse lymphoma cells>, Product Details of C7H17Cl2N2O3P, the main research area is cyclophosphamide monohydrate cytotoxicity human lymphocyte TK lymphoma cell.

The study was conducted to evaluate and compare the cytotoxicity of cyclophosphamide monohydrate in In vitro Mammalian Chromosome Aberration Test (CAT) using cultured healthy human whole blood lymphocytes and In vitro Cell Gene Mutation Assay (CGM) using L5178Y TK+/- mouse lymphoma cells as per OECD guidelines Number 473 & 476 resp., both in the presence (2%volume/volume) and absence of metabolic activation system. Cyclophosphamide monohydrate is cytotoxic at the doses 250, 125, 62.5, 31.25 μg/mL and non-cytotoxic at 15.62 μg/mL in CGM, where 250, 125, 62.5 μg/mL of doses are cytotoxic and 31.25, 15.62 μg/mL doses are non-cytotoxic in CAT, in the presence of metabolic activation system. Cytotoxicity was not observed in all the test doses 250, 125, 62.5, 31.25, 15.62 μg/mL, in the absence of metabolic activation system both in CGM and CAT. Cyclophosphamide monohydrates require metabolic activation for its cytotoxicity. A lower dose of cyclophosphamide monohydrate is cytotoxic in In vitro Cell Gene Mutation Assay (CGM) than Mammalian Chromosome Aberration Test (CAT) In vitro. Cyclophosphamide monohydrate is non cytotoxic in both assays, in the absence of metabolic activation system indicates that metabolic activation system play a key role in the cytotoxicity of cyclophosphamide monohydrate.

World Journal of Pharmacy and Pharmaceutical Sciences published new progress about Antitumor agents. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Product Details of C7H17Cl2N2O3P.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Negishi, Akio; Oshima, Shinji; Horii, Norimitsu; Mutoh, Mizue; Inoue, Naoko; Numajiri, Sachihiko; Ohshima, Shigeru; Kobayashi, Daisuke published the artcile< Adverse drug events caused by drugs contraindicated for coadministration reported in the Japanese adverse drug event report database and recognized by reporters>, Category: chlorides-buliding-blocks, the main research area is human adverse drug event report database coadministration.

The “”INTERACTIONS”” section of package inserts aims to provide alert-type warnings in clin. practice; however, these also include many drug-drug interactions that occur rarely. Moreover, considering that drug-drug interaction alert systems were created based on package inserts, repeated alerts can lead to alert fatigue. Although investigations have been conducted to determine prescriptions that induce drug-drug interactions, no studies have focused explicitly on the adverse events induced by drug-drug interactions. We, therefore, sought to investigate the true occurrence of adverse events caused by drug pair contraindications for coadministration in routine clin. practice. Toward this, we created a list of drug combinations that were designated as “”contraindications for coadministration”” and extracted the cases of adverse drug events from the Japanese Adverse Drug Event Report database that occurred due to combined drug usage. We then calculated the reporters’ recognition rate of the drug-drug interactions. Out of the 2121 investigated drug pairs, drug-drug interactions were reported in 43 pairs, 23 of which included an injected drug and many included catecholamines. Warfarin potassium and miconazole (19 reports), azathioprine and febuxostat (11 reports), and warfarin potassium and iguratimod (six reports) were among the 20 most-commonly reported oral medication pairs that were contraindicated for coadministration, for which recognition rates of drug-drug interactions were high. Although these results indicate that only a few drug pair contraindications for coadministration were associated with adverse drug events (43 pairs out of 2121 pairs), it remains necessary to translate these findings into clin. practice.

Biological & Pharmaceutical Bulletin published new progress about Clinical practice guidelines. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Zhou, Qingxin; Lin, Meihua; Feng, Xing; Ma, Fei; Zhu, Yuekun; Liu, Xing; Qu, Chao; Sui, Hong; Sun, Bei; Zhu, Anlong; Zhang, Heng; Huang, He; Gao, Zhi; Zhao, Yongxiang; Sun, Jiangyun; Bai, Yuxian; Jin, Junfei; Hong, Xuehui; Zou, Chang; Zhang, Zhiyong published the artcile< Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism>, Related Products of 6055-19-2, the main research area is cholangiocarcinoma CLK3 serine threonine tyrosine nucleotide metabolism.

CDC-like kinase 3 (CLK3) is a dual specificity kinase that functions on substrates containing serine/threonine and tyrosine. But its role in human cancer remains unknown. Herein, we demonstrated that CLK3 was significantly up-regulated in cholangiocarcinoma (CCA) and identified a recurrent Q607R somatic substitution that represented a gain-of-function mutation in the CLK3 kinase domain. Gene ontol. term enrichment suggested that high CLK3 expression in CCA patients mainly was associated with nucleotide metabolism reprogramming, which was further confirmed by comparing metabolic profiling of CCA cells. CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes. Notably, the CCA-associated CLK3-Q607R mutant induced USP13-Y708 phosphorylation and enhanced the activity of c-Myc. In turn, c-Myc transcriptionally up-regulated CLK3. Finally, we identified tacrine hydrochloride as a potential drug to inhibit aberrant CLK3-induced CCA. These findings demonstrate that CLK3 plays a crucial role in CCA purine metabolism, suggesting a potential therapeutic utility.

Journal of Experimental Medicine published new progress about Cell infiltration. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Related Products of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Qin, Hongwei; Gao, Qingdong; Niu, Huiming; Wang, Zhefeng; Zhu, Xiaolin; Li, Jinlian; Yuan, Xing; Wu, Dongmei published the artcile< An in situ electrochemical detection method of cell viability>, Quality Control of 6055-19-2, the main research area is electrochem electrode cell viability culture.

An in situ electrochem. method of cell viability, which integrated cell culture, pretreatment and detection in a cell culture dish, was developed. The method significantly improved the electrochem. response of cells, simplified the operation process, reduced the experiment time, avoided the use of trypsin, and was applied in the study of the effectiveness of antitumor drugs on tumor suppression.

Analyst (Cambridge, United Kingdom) published new progress about Animal tissue culture. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Quality Control of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Jung, Hyun Joo; Chen, Zheng; Fayad, Luis; Wang, Michael; Romaguera, Jorge; Kwak, Larry W.; McCarty, Nami published the artcile< Bortezomib-resistant nuclear factor κB expression in stem-like cells in mantle cell lymphoma>, COA of Formula: C7H17Cl2N2O3P, the main research area is bortezomib resistance NFkappaB stem like mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a subtype of B-cell Non-Hodgkin’s Lymphoma (NHL) and accounts for approx. 6% of all lymphomas. Unlike small lymphocytic lymphoma and chronic lymphocytic lymphoma, which are relatively sensitive to chemotherapy, MCL is highly refractory to most chemotherapy, and has the worst survival rate among NHL patients. Stem-like cells in MCL, which we have termed mantle cell lymphoma-initiating cells (MCL-ICs), enriched in the population that are lack of prototypic B-cell marker CD19. These cells were able to self-renew upon serial transplantation and are highly tumorigenic. Importantly, these stem-like cells confer chemotherapeutic resistance to MCL. In this report, we show that stem-like MCL-ICs are resistant to bortezomib, as well as chemotherapeutic regimens containing bortezomib, despite constitutive nuclear factor-κB (NF-κB) expression. Interestingly, bortezomib treatment induced MCL-IC differentiation in plasma-like cells with upregulated expression of CD38 and CD138. This process was accompanied by expression of plasma cell differentiation transcriptional factors, BLIMP-1 and IRF4. This article is the first to show that stem-like MCL cells utilize constitutive NF-κB expression for survival. Given that the NF-κB expression in MCL-ICs is resistant to bortezomib, it will be important to find alternative therapeutic strategies to inhibit NF-κB expression.

Experimental Hematology (New York, NY, United States) published new progress about Antitumor agent resistance. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, COA of Formula: C7H17Cl2N2O3P.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Polard, T.; Jean, S.; Merlina, G.; Laplanche, C.; Pinelli, E.; Gauthier, L. published the artcile< Giemsa versus acridine orange staining in the fish micronucleus assay and validation for use in water quality monitoring>, Name: 2-(Bis(2-chloroethyl)amino)-1,3,2-oxazaphosphinane 2-oxide hydrate, the main research area is staining micronucleus assay acridine orange Giemsa water monitoring Carassius.

This study concerns a comparative anal. of the acridine orange and Giemsa staining procedures for the fish erythrocyte micronucleus assay. The goal was to optimize the assay in the context of field water monitoring. Fish (Carassius carassius) were exposed to a reference genotoxic agent, cyclophosphamide monohydrate 5 mg L-1 for 2, 4, and 6 days before testing. Slides from each individual were scored using the two procedures. The results show that the assay was more sensitive when acridine orange was used. When slides were Giemsa stained, the presence of ambiguous artifacts, leading to false positives and increasing random variance, reduced the contrast between exposed and control samples. Acridine Orange staining was then applied in the context of water quality monitoring. Fish were exposed for 4 days to water sampled in two hydrol. contexts: basal flow and spring flood. The results show that exposure to spring flood water in an agricultural stream can induce mutagenicity.

Ecotoxicology and Environmental Safety published new progress about Aquatic toxicity. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Name: 2-(Bis(2-chloroethyl)amino)-1,3,2-oxazaphosphinane 2-oxide hydrate.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Mukherjee, N.; Delay, E. R. published the artcile< Cyclophosphamide-induced disruption of umami taste functions and taste epithelium>, COA of Formula: C7H17Cl2N2O3P, the main research area is cyclophosphamide monohydrate taste bud epithelium monosodium glutamate IMP.

Clin. studies have reported taste dysfunctions developing in patients undergoing chemotherapy. This adverse side effect is a major concern for the doctors and patients because disrupted taste can reduce appetite, cause malnutrition, delay recovery, and affect quality of life. Cyclophosphamide (CYP) is a common atenoplastic drug used during chemotherapy and is thought to affect taste through learned tasted aversions. This study asked whether CYP also alters umami taste sensory functions and disrupts taste epithelium of mice. Behavioral tests focused on taste acuity, assessed by the ability of mice to discriminate between the taste qualities of two umami substances, monosodium glutamate (MSG) and IMP, and taste sensitivity, assessed by detection thresholds of MSG and IMP, after an IP injection (75 mg/kg) of CYP. The behavioral results revealed a two-phase disturbance in taste acuity and loss of sensitivity, the first phase occurring within 2-4 days after injection and the second occurring 9-12 days after injection. The number of fungiform papillae (with and without pores) decreased immediately after injection and did not begin to recover until 12 days after injection. Circumvallate taste buds began to show disturbances by 8 days after injection and evidence of recovery beginning 12 days after injection. Von Ebner glands were smaller and secreted less saliva 4 days postinjection but not later. These findings suggest the initial behavioral deficits may be because of cytotoxic effects of the drug on taste sensory tissues, whereas the second phase may be because of a disturbance of the taste cell replacement cycle.

Neuroscience (Amsterdam, Netherlands) published new progress about Body weight. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, COA of Formula: C7H17Cl2N2O3P.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Hakura, Atsushi; Hori, Yuji; Uchida, Kanako; Sawada, Shigeki; Suganuma, Akiyoshi; Aoki, Toyohiko; Tsukidate, Kazuo published the artcile< Inhibitory effect of dimethyl sulfoxide on the mutagenicity of promutagens in the Ames test>, Name: 2-(Bis(2-chloroethyl)amino)-1,3,2-oxazaphosphinane 2-oxide hydrate, the main research area is dimethyl sulfoxide promutagen mutagenicity inhibition detoxification.

The effect of DMSO on the mutagenicity of 14 promutagens belonging to several chem. classes and one direct mutagen as a reference compound was examined in the Ames preincubation test, to clarify how much the test results were affected by its inhibitory activity on metabolic enzymes. The mutagens were assayed by the preincubation method using the TA100 or WP2uvrA (pKM101) bacterial test strains in the presence of 1% and 14% DMSO (concentrations in treatment mixture) with S9 mix for 12 promutagens that are known to be activated by CYP enzymes or without S9 mix for 2 promutagens that are known to be activated by bacterial nitroreductase enzymes, and the direct-mutagen. The data indicate that the mutagenicity of 11 of the 14 promutagens was significantly reduced in the presence of 14% DMSO as compared with that in the presence of 1% DMSO, while the 3 remaining promutagens and the direct mutagen exhibited mutagenicity of equal degree at both concentrations The largest inhibitory effect of DMSO was found on the nitrosamines in WP2uvrA(pKM101) and TA100, and no cytotoxicity was detected by survival test, with 14% DMSO in WP2uvrA(pKM101), at any amounts of dimethylnitrosamine. Further equivalent or slightly lower cytotoxicity in the presence of 14% DMSO than in the presence of 1% DMSO was detected by decrease in the bacterial background-lawn d., as a whole. These observations suggest that the reduction in the yield of revertant colonies in the presence of 14% DMSO with the 11 chems. was not due to cytotoxicity of DMSO. The inhibitory effect of DMSO on the mutagenicity of the promutagens can be explained by its inhibitory effect on the drug-metabolizing enzymes involved in the activation/detoxification pathways. Use of DMSO at a low concentration, such as 1%, may be suggested for the Ames test, as for other in vitro genotoxicity tests.

Genes and Environment published new progress about Biological detoxification. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Name: 2-(Bis(2-chloroethyl)amino)-1,3,2-oxazaphosphinane 2-oxide hydrate.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics