Category: 6055-19-2

Imatoh, Takuya; Ushiki, Atsuhito; Ota, Masao; Ito, Michiko; Sekine, Akihiro; Yamashita, Taiki; Mashimo, Yoichi; Nakamura, Ryosuke; Saito, Kosuke; Saito, Yoshiro; Hanaoka, Masayuki published the artcile< Association of HLA-DRB1*04:05 allele with drug-induced interstitial lung disease in Japanese population>, Category: chlorides-buliding-blocks, the main research area is DRB HLA bevacizumab fluorouracil interstitial lung disease population.

Drug-induced interstitial lung disease (DILD) is a life-threatening adverse reaction. The Japanese population is more susceptible to DILD as compared with other populations, suggesting its pathogenesis could vary depending on ethnic genetic background. We conducted case-control studies to elucidate the association between DILD and HLA alleles in the Japanese. The 177 clin. diagnosed DILD patients and 3002 healthy controls for exploration and 55 DILD patients and 201 healthy controls for validation were genotyped for four HLA genes. HLA-DRB1*04:05 was significantly associated with DILD (corrected p = 0.014); this was also validated in the other set of patients/controls. Chem. drugs other than protein therapeutics showed this association (p = 1.7 x 10-4) . The Japanese population showed a higher HLA-DRB1*04:05 frequency than most other populations. In conclusion, HLA-DRB1*04:05 could be associated with DILD susceptibility in Japanese individuals, and its high general frequency may explain the high reported incidence of DILD in Japanese.

Pharmacogenomics Journal published new progress about Age groups. 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

Ageberg, Malin; Rydstroem, Karin; Relander, Thomas; Drott, Kristina published the artcile< The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death>, Related Products of 6055-19-2, the main research area is HDAC inhibitor valproic acid B cell lymphoma antitumor apoptosis; rituximab cyclophosphamide doxorubicin monohydrate vincristine sulfate prednisone; HDAC; Non-Hodgkins lymphoma; valproate; valproic acid.

Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematol. malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60 % of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC inhibitor valproic acid (VPA) on DLBCL cell lines. To elucidate the effects of VPA on chemo-sensitivity, we used a cell-line based model of CHOP-refractory DLBCL. All five DLBCL cell lines treated with VPA alone or in combination with CHOP showed decreased viability and proliferation. The VPA-induced sensitization of DLBCL cells to cytotoxic treatment resulted in increased number of apoptotic cell as judged by annexin V-positivity and the presence of cleaved caspase-3. In addition, pretreatment with VPA resulted in a significantly increased DNA-damage as compared to CHOP alone. In summary, HDAC inhibitors such as VPA, are promising therapeutic agents in combination with R-CHOP for patients with DLBCL.

American Journal of Translational Research published new progress about Acetylation. 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

Misik, Miroslav; Pichler, Clemens; Rainer, Bernhard; Filipic, Metka; Nersesyan, Armen; Knasmueller, Siegfried published the artcile< Acute toxic and genotoxic activities of widely used cytostatic drugs in higher plants: Possible impact on the environment>, Reference of 6055-19-2, the main research area is Tradescantia Allium genotoxicity cytotoxicity; Allium; Cytostatics; EC(50); Micronuclei; Tradescantia.

Cytostatic drugs are highly toxic pharmaceuticals and it was repeatedly postulated that they may cause adverse effects in ecosystems. The acute toxic and genotoxic properties of these drugs have not been adequately investigated in higher plants so far; therefore, we studied the most widely used drugs (5-flurouracil, 5FU; etoposide, Et; cisplatin, CisPt; carboplatin, CaPt; vincristine sulfate, VinS and cyclophosphamide monohydrate, CP) in micronucleus (MN) assays with meiotic pollen tetrad cells of Tradescantia and with root cells from Allium cepa. MNi are formed as a consequence of chromosome breaks and aneuploidy. We monitored also the acute toxic properties of the drugs, i.e. inhibition of cell division (mitotic indexes and retardation of root growth) in the latter species. All compounds caused in both indicator plants genotoxic effects. The order of genotoxic potencies expressed as NOELs in μM was CisPt (0.1)≥Et (0.5)>CP (1.0)>CaPt (10)>5FU (30)>VinS (100) in Tradescantia. A similar order was seen in Allium MN but Et was less active (5.0 μM). Four compounds caused alterations of the mitotic indexes under the present conditions namely CisPt (0.5), Et (10.0), 5FU (10.0) and VinS (100). Inhibition of root growth decreased in the order CisPt (0.5)>Et (1.0)≥VinS (1.0)>5FU (5.0)>CaPt (33.0)>CP (>1000). Comparisons of the NOELs with the predicted environmental concentrations (PEC) show that the latter values are at least 5 orders of magnitude lower and indicate that it is unlikely that their release in the environment may cause adverse effects in higher plants. However, it is notable that the levels of both platinum compounds and of 5FU in hospital effluents may reach levels which may induce damage of the genetic material.

Environmental Research published new progress about Acute toxicity. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Reference of 6055-19-2.

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

Wiesner, Jochen; Ziemann, Christina; Hintz, Martin; Reichenberg, Armin; Ortmann, Regina; Schlitzer, Martin; Fuhst, Rainer; Timmesfeld, Nina; Vilcinskas, Andreas; Jomaa, Hassan published the artcile< FR-900098, an antimalarial development candidate that inhibits the non-mevalonate isoprenoid biosynthesis pathway, shows no evidence of acute toxicity and genotoxicity>, COA of Formula: C7H17Cl2N2O3P, the main research area is toxicol antimalarial drug; Ames test; FR-900098; Plasmodium falciparum; acute toxicity; drug development; fosmidomycin; genotoxicity; malaria; micronucleus test; mouse lymphoma assay.

FR-900098 is an inhibitor of 1-deoxy-D-xylulose-5-phosphate (DXP) reductoisomerase, the second enzyme in the non-mevalonate isoprenoid biosynthesis pathway. In previous studies, FR-900098 was shown to possess potent antimalarial activity in vitro and in a murine malaria model. In order to provide a basis for further preclin. and clin. development, we studied the acute toxicity and genotoxicity of FR-900098. We observed no acute toxicity in rats, i.e. there were no clin. signs of toxicity and no substance-related deaths after the administration of a single dose of 3000 mg/kg body weight orally or 400 mg/kg body weight i.v. No mutagenic potential was detected in the Salmonella typhimurium reverse mutation assay (Ames test) or an in vitro mammalian cell gene mutation test using mouse lymphoma L5178Y/TK+/- cells (clone 3.7.2C), both with and without metabolic activation. In addition, FR-900098 demonstrated no clastogenic or aneugenic capability or significant adverse effects on blood formation in an in vivo micronucleus test with bone marrow erythrocytes from NMRI mice. We conclude that FR-900098 lacks acute toxicity and genotoxicity, supporting its further development as an antimalarial drug.

Virulence published new progress about Antimalarials. 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

Andersson, M.; Aronsson, P.; Giglio, D.; Wilhelmson, A.; Jerabek, P.; Tobin, G. published the artcile< Pharmacological modulation of the micturition pattern in normal and cyclophosphamide pre-treated conscious rats>, Reference of 6055-19-2, the main research area is micturition nitric oxide muscarinic receptor cyclophosphamide monohydrate.

In the current study, we wanted to assess the influence of muscarinic receptors, nitric oxide and purinoceptors on the micturition pattern of conscious normal and cyclophosphamide (CYP) pre-treated rats. The micturition parameters were assessed using a metabolic cage. Rats were pre-treated with either saline or CYP, to induce cystitis, followed by treatment with either the muscarinic M1/M3/M5 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), the nitric oxide synthase blocker Nω-nitro-L-arginine Me (L-NAME), the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) or a combination of 4-DAMP with PPADS or L-NAME. Voiding volumes per micturition event were significantly lower in CYP pre-treated than in saline pre-treated rats. Neither 4-DAMP nor L-NAME had any effect in the normal rats, whereas PPADS reduced the micturition volume per event. In CYP pre-treated rats, 4-DAMP and L-NAME significantly increased voiding volumes per event and micturition frequency, resp. 4-DAMP dose-dependently reduced the differences in micturition activity between saline and CYP pre-treated rats. We show that cystitis changes the urodynamics in conscious rats and that this change seems to depend on the production of NO and on altered muscarinic receptor effects. The altered muscarinic receptor responses are likely to per se involve NO-mediated mechanisms.

Autonomic Neuroscience published new progress about Bladder. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Reference of 6055-19-2.

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

Nagahori, Hirohisa; Suzuki, Noriyuki; Le Coz, Florian; Omori, Takashi; Saito, Koichi published the artcile< Prediction of in vivo developmental toxicity by combination of Hand1-Luc embryonic stem cell test and metabolic stability test with clarification of metabolically inapplicable candidates>, Formula: C7H17Cl2N2O3P, the main research area is development toxicity risk assessment Hand Luc embryo stem cell; Cytotoxicity; In-vitro toxicity; Metabolism; Reproductive toxicity.

Hand1-Luc Embryonic Stem Cell Test (Hand1-Luc EST) is a promising alternative method for evaluation of developmental toxicity. However, the problems of predictivity have remained due to appropriateness of the solubility, metabolic system, and prediction model. Therefore, we assessed the usefulness of rat liver S9 metabolic stability test using LC-MS/MS to develop new prediction model. A total of 71 chems. were analyzed by measuring cytotoxicity and differentiation toxicity, and highly reproducible (CV = 20%) results were obtained. The first prediction model was developed by discriminant anal. performed on a full dataset using Hand1-Luc EST, and 66.2% of the chems. were correctly classified by the cross-validated classification. A second model was developed with addnl. descriptors obtained from the metabolic stability test to calculate hepatic availability, and an accuracy of 83.3% was obtained with applicability domain of 50.7% (=36/71) after exclusion of 22 metabolically inapplicable candidates, which potentially have a metabolic activation property. A step-wise prediction scheme with combination of Hand1-Luc EST and metabolic stability test was therefore proposed. The current results provide a promising in vitro test method for accurately predicting in vivo developmental toxicity.

Toxicology Letters published new progress about Animal gene Role: BUU (Biological Use, Unclassified), BIOL (Biological Study), USES (Uses) (HAND1). 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

Ofengeim, Dimitry; Shi, Peng; Miao, Benchun; Fan, Jing; Xia, Xiaofeng; Fan, Yubo; Lipinski, Marta M.; Hashimoto, Tadafumi; Polydoro, Manuela; Yuan, Junying; Wong, Stephen T. C.; Degterev, Alexei published the artcile< Identification of Small Molecule Inhibitors of Neurite Loss Induced by Aβ peptide using High Content Screening>, Computed Properties of 6055-19-2, the main research area is non steroidal antiinflammatory drug amyloid beta neurite Alzheimers disease.

Multiple lines of evidence indicate a strong relationship between Aβ peptide-induced neurite degeneration and the progressive loss of cognitive functions in Alzheimer disease (AD) patients and in AD animal models. This prompted us to develop a high content screening assay (HCS) and Neurite Image Quantitator (NeuriteIQ) software to quantify the loss of neuronal projections induced by Aβ peptide neurons and enable us to identify new classes of neurite-protective small mols., which may represent new leads for AD drug discovery. We identified thirty-six inhibitors of Aβ-induced neurite loss in the 1,040-compound National Institute of Neurol. Disorders and Stroke (NINDS) custom collection of known bioactives and FDA approved drugs. Activity clustering showed that non-steroidal anti-inflammatory drugs (NSAIDs) were significantly enriched among the hits. Notably, NSAIDs have previously attracted significant attention as potential drugs for AD; however their mechanism of action remains controversial. Our data revealed that cyclooxygenase-2 (COX-2) expression was increased following Aβ treatment. Furthermore, multiple distinct classes of COX inhibitors efficiently blocked neurite loss in primary neurons, suggesting that increased COX activity contributes to Aβ peptide-induced neurite loss. Finally, we discovered that the detrimental effect of COX activity on neurite integrity may be mediated through the inhibition of peroxisome proliferator-activated receptor γ (PPARγ) activity. Overall, our work establishes the feasibility of identifying small mol. inhibitors of Aβ-induced neurite loss using the NeuriteIQ pipeline and provides novel insights into the mechanisms of neuroprotection by NSAIDs.

Journal of Biological Chemistry published new progress about Alzheimer disease. 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Computed Properties of 6055-19-2.

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

Pointon, Joanna C.; Eagle, Gina; Bailey, James; Evans, Paul; Allsup, David; Greenman, John published the artcile< Thalidomide enhances cyclophosphamide and dexamethasone-mediated cytotoxicity towards cultured chronic lymphocytic leukaemia cells>, Quality Control of 6055-19-2, the main research area is cytotoxic thalidomide cyclophosphamide monohydrate dexamethasone chronic lymphocytic leukemia.

Numerous chemotherapeutic regimens exist for the treatment of symptomatic or progressive chronic lymphocytic leukemia (CLL). However, once the disease becomes refractory to nucleoside-based therapy the prognosis is poor. In this study we investigated the cytotoxicity of thalidomide in combination with dexamethasone, fludarabine and cyclophosphamide. Cells from a cohort of 25 CLL patients were incubated for 72 h with each of these three agents, at 3 concentrations, both with and without thalidomide. Cell viability was assessed using the Annexin V:FITC assay. Fludarabine was highly toxic to the cells, producing very high levels of cell death; however, thalidomide did not increase this effect. Cyclophosphamide combined with thalidomide showed a small, non-significant improvement in toxicity compared with monotherapy. Median cell death for 5 μM dexamethasone monotherapy and for combination with thalidomide was 15% [interquartile range (IQR) 0-38%] and 17% (IQR 0-54%), resp. (Wilcoxon Signed Rank anal., p = 0.034). Cell death for 10 μM dexamethasone monotherapy was 15% (IQR 0-45%) and 16% (IQR 0-62%) in combination with thalidomide (Wilcoxon Signed Rank anal., p = 0.035). At the highest doses tested 11 of 25 cases displayed an enhancement of cyclophosphamide-mediated cytotoxicity, and 14 of 25 cases showed enhanced dexamethasone-mediated cytotoxicity in the presence of thalidomide. Some CLL cells in which dexamethasone-mediated killing was enhanced were derived from patients with poor prognostic markers, including p53 mutations and unmutated IgVH genes. In summary, thalidomide enhances cyclophosphamide- and dexamethasone-mediated cytotoxicity of CLL cells in vitro in a proportion of cases.

Oncology Reports published new progress about CD19 antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Shand, F. L.; Howard, J. G. published the artcile< Induction in vitro of reversible immunosuppression and inhibition of B cell receptor regeneration by defined metabolites of cyclophosphamide>, Reference of 6055-19-2, the main research area is lymphocyte Ig cyclophosphamide metabolite immunosuppression; receptor lymphocyte cyclophosphamide metabolite immunosuppression.

A number of defined metabolites and derivatives of cyclophosphamide (I) [50-18-0] were compared with the parent compound for their capacity to induce suppression of humoral antibody responses in vivo and in vitro and to inhibit the regeneration of surface Ig (sIg) receptors on B cells subsequent to capping with anti-Ig serum. Both functions were inhibited by exposing spleen cells in vitro to the most active compounds (4-hydroperoxycyclophosphamide [39800-16-3] and phosphoramide mustard [10159-53-2]) in concentrations of ≤10 μg/mL. Although these inhibitory activities were restricted to those mols. with demonstrable alkylating activity, they are nevertheless reversible and not dependent on events leading to cell death. Inhibition with microsomally activated I in vitro rendered splenic B cells hypersusceptible to tolerance induction by levan, although in the absence of this antigen they recovered full responsiveness to it within 7-10 days. Since lethally irradiated mice repopulated with adult bone marrow cells do not regenerate normal responsiveness to polysaccharide antigens in <50-100 days, the rapid recovery by I-treated spleen cells probably involves reversal of suppression in B cells and not renewal from stem cells. The previous proposal that impairment of B cell receptor regeneration by I is causally related to its capacity to promote B cell tolerance induction by thymus-independent antigens is supported. European Journal of Immunology published new progress about Antibodies and Immunoglobulins Role: BIOL (Biological Study). 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Reference of 6055-19-2.

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

Logsdon, Amanda L.; Herring, Betty J.; Lockard, Jarrett E.; Miller, Brittany M.; Kim, Hanna; Hood, Ronald D.; Bailey, Melissa M. published the artcile< Exposure to Green Tea Extract Alters the Incidence of Specific Cyclophosphamide-Induced Malformations>, Category: chlorides-buliding-blocks, the main research area is green tea extract cyclophosphamide monohydrate teratogenicity fetus natural pharmaceutical.

BACKGROUND: Green tea extract (GTE) has been shown to have antioxidative properties due to its high content of polyphenols and catechin gallates. Previous studies indicated that catechin gallates scavenge free radicals and attenuate the effects of reactive oxygen species. Cyclophosphamide (CP) produces reactive oxidative species, which can have adverse effects on development, causing limb, digit, and cranial abnormalities. The current study was performed to determine if exposure to GTE can decrease teratogenic effects induced by CP in CD-1 mice. METHODS: From gestation days (GD) 6-13, mated CD-1 mice were dosed with 400 or 800 mg/kg/d GTE; 100, 200, 400, or 800 mg/kg/d GTE + CP; CP alone, or the vehicle. GTE was given by gavage. CP (20 mg/kg) was given by i.p. injection on GD 10. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. RESULTS: The highest GTE dose did not effectively attenuate, and in some cases exacerbated the neg. effect of CP. GTE alone was also associated with an increased incidence of microblepharia. Conversely, moderate GTE doses (200 and/or 400 mg/kg/d) attenuated the effect of CP on fetal weight and (GTE 200 mg/kg/d) decreased the incidences of certain defects resulting from CP exposure. CONCLUSIONS: Exposure of a developing mammal to moderate doses of GTE can modulate the effects of exposure to CP during development, possibly by affecting biotransformation, while a higher GTE dose tended to exacerbate the developmental toxicity of CP. GTE alone appeared to cause an adverse effect on eyelid development.

Birth Defects Research, Part B: Developmental and Reproductive Toxicology published new progress about Arm. 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