Category: 1750-45-4

Reference of 1750-45-4, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.1750-45-4, Name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, molecular formula is C7H4ClNO3. In a article£¬once mentioned of 1750-45-4

Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-Ligase Genetic Ablation in Mice: Therapeutic and toxicological relevance

The hepatic endoplasmic reticulum (ER)?anchored monotopic proteins, cytochromes P450 (P450s), are enzymes that metabolize endobiotics (physiologically active steroids and fatty acids), as well as xenobiotics including therapeutic/chemotherapeutic drugs, nutrients, carcinogens, and toxins. Alterations of hepatic P450 content through synthesis, inactivation, or proteolytic turnover influence their metabolic function. P450 proteolytic turnover occurs via ER-associated degradation (ERAD) involving ubiquitin (Ub)-dependent proteasomal degradation (UPD) as a major pathway. UPD critically involves P450 protein ubiquitination by E2/E3 Ub-ligase complexes. We have previously identified the ER-polytopic gp78/AMFR (autocrine motility factor receptor) as a relevant E3 in CYP3A4, CYP3A23, and CYP2E1 UPD. We now document that liver-conditional genetic ablation of gp78/ AMFR in male mice disrupts P450 ERAD, resulting in statistically significant stabilization of Cyp2a5 and Cyp2c, in addition to that of Cyp3a and Cyp2e1. More importantly, we establish that such stabilization is of the functionally active P450 proteins, leading to corresponding statistically significant enhancement of their drug-metabolizing capacities. Our findings, with clinically relevant therapeutic drugs (nicotine, coumarin, chlorzoxazone, and acetaminophen) and the prodrug (tamoxifen) as P450 substrates, reveal that P450 ERAD disruption could influence therapeutic drug response and/or toxicity, warranting serious consideration as a potential source of clinically relevant drug-drug interactions (DDIs). Because gp78/AMFR is not only an E3 Ub-ligase, but also a cell-surface prometastatic oncogene that is upregulated in various malignant cancers, our finding that hepatic gp78/AMFR knockout can enhance P450-dependent bioactivation of relevant cancer chemotherapeutic prodrugs is of therapeutic relevance and noteworthy in prospective drug design and development.

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Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

1750-45-4, Name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, belongs to benzoxazole compound, is a common compound. COA of Formula: C7H4ClNO3In an article, once mentioned the new application about 1750-45-4.

Effects of catalpol on the activity of human liver cytochrome P450 enzymes

1. Catalpol possesses numerous pharmacological activities, and however, little data available for the effects of catalpol on the activity of human liver cytochrome P450 (CYP) enzymes. 2. This study investigates the inhibitory effects of catalpol on the main human liver CYP isoforms. In this study, the inhibitory effects of catalpol on the eight human liver CYP isoforms 1A2, 2A6, 2E1, 2D6, 2C9, 2C19, 2C8 and 3A4 were investigated in human liver microsomes. 3. The results indicated that catalpol could inhibit the activity of CYP3A4, CYP2E1 and CYP2C9, with IC50 values of 14.27, 22.4 and 14.69 muM, respectively, but those other CYP isoforms were not affected. Enzyme kinetic studies showed that catalpol was not only a noncompetitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1 and CYP2C9, with Ki values of 7.40, 10.75 and 7.37 muM, respectively. In addition, catalpol is a time-dependent inhibitor for CYP3A4, with maximum inactivation (kinact) and 50% maximum inactivation (KI) values of 0.02 min?1 and 1.86 muM, respectively. 4. The in vitro studies of catalpol with CYP isoforms suggest that catalpol has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2C9. Further in vivo studies are needed in order to evaluate the significance of this interaction.

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Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Application of 1750-45-4, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.1750-45-4, Name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, molecular formula is C7H4ClNO3. In a article£¬once mentioned of 1750-45-4

Hepatic expression of cytochrome P450 in Zucker diabetic fatty rats

In this study, the hepatic expression of cytochrome P450 (CYP) enzymes, including CYP1A1/2, 2B1, 2C11, 2E1, 3A1/2, and 4A, was investigated in 5-week-old (insulinresistant state) and 11-week-old (diabetic) Zucker diabetic fatty (ZDF) rats. Serum glucose and glycated hemoglobin levels were increased in 11-week-old ZDF rats, but not in 5-weekold ZDF rats. Hyperinsulinemia was observed in both age groups. The microsomal protein, total CYP, CYP reductase, CYP1A1/2, and CYP3A1 levels did not differ between 5- and 11-week-old ZDF rats and their respective control rats, while CYP4A was up-regulated in both groups. Hepatic levels of cytochrome b5, CYP2B1, CYP2C11, CYP2E1, and CYP3A2 were decreased in 5-week-old ZDF rats, but not in 11-week-old ZDF rats. Similarly, pentoxyresorufin O-depentylase, testosterone 2alpha- and 16alpha-hydroxylase, chlorzoxazone 6- hydroxylase, and midazolam 1?- and 4-hydroxylase activities were decreased only in 5-weekold ZDF rats. Based on these results, the 5-week-old ZDF rats exhibited down-regulation of the major CYP enzymes. These results suggest that hepatic expression of CYP enzymes may be dysregulated during development in ZDF rats. With the exception of CYP2B1 and CYP4A, the hepatic levels and activities of CYP were comparable between 11-week-old ZDF and control rats, suggesting that xenobiotic metabolism is normally regulated in the early diabetic state.

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Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Related Products of 1750-45-4, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Review, and a compound is mentioned, 1750-45-4, 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, introducing its new discovery.

A comprehensive review of cytochrome P450 2E1 for xenobiotic metabolism

Cytochrome P450 2E1 (CYP2E1) plays a vital role in drug-induced hepatotoxicity and cancers (e.g. lung and bladder cancer), since it is responsible for metabolizing a number of medications and environmental toxins to reactive intermediate metabolites. CYP2E1 was recently found to be the highest expressed CYP enzyme in human livers using a proteomics approach, and CYP2E1-related toxicity is strongly associated with its protein level that shows significant inter-individual variability related to ethnicity, age, and sex. Furthermore, the expression of CYP2E1 demonstrates regulation by extensive genetic polymorphism, endogenous hormones, cytokines, xenobiotics, and varying pathological states. Over the past decade, the knowledge of pharmacology, toxicology, and biology about CYP2E1 has grown remarkably, but the research progress has yet to be summarized. This study presents a timely systematic review on CYP2E1?s xenobiotic metabolism, genetic polymorphism, and inhibitors, with the focus on their clinical relevance for the efficacy and toxicity of various CYP2E1 substrates. Moreover, several knowledge gaps have been identified towards fully understanding the potential interactions among different CYP2E1 substrates in clinical settings. Through in-depth analyses of these knowns and unknowns, we expect this review will aid in future drug development and improve management of CYP2E1 related clinical toxicity.

Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Related Products of 1750-45-4. In my other articles, you can also check out more blogs about 1750-45-4

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Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

One of the major reasons for studying chemical kinetics is to use measurements of the macroscopic properties of a system, Recommanded Product: 1750-45-4, such as the rate of change in the concentration of reactants or products with time.In a article, mentioned the application of 1750-45-4, Name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, molecular formula is C7H4ClNO3

Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans

Disulfiram (DSF) is a mechanism-based inhibitor of cytochrome P-450 2E1 (CYP2E1), resulting in loss of CYP2E1 protein and activity, which may be useful in preventing CYP2E1-mediated xenobiotic toxicity. The duration of inhibition after a single DSF dose is, however, unknown. The purpose of this investigation was to determine this duration, and CYP2E1 formation and degradation rates, in humans. Oral chlorzoxazone (CLZ) was used as the selective in vivo probe for CYP2E1. Healthy subjects received CLZ to determine baseline CYP2E1 activity (CLZ plasma clearance and 6- hydroxychlorzoxazone fractional metabolic clearance). One week later, DSF (500 mg orally) was administered at bedtime, and CLZ administered the following morning and 3, 6, 8, 10, and 13 days after DSF. A terminal DSF metabolite, 2-thiothiazolidine-4 carboxylic acid, was also measured in each 24-h urine sample. The mean CLZ clearance and 6-hydroxychlorzoxazone fractional metabolic clearance on the first day declined to 10.2 and 5.5% of baseline values, indicating rapid and profound CYP2E1 inhibition. CYP2E1 activity returned to half that of control on day 3, and to baseline values on day 8. Assuming zero-order synthesis and first-order degradation, the in vivo CYP2E1 synthesis rate and degradation half-life was estimated to be 11 ¡À 5 nmol/h and 50 ¡À 19 h, respectively. Significant amounts of 2- thiothiazolidine-4 carboxylic acid were present only on day 1, suggesting that the return of in vivo CYP2E1 activity was not caused by inhibitor washout, but by enzyme resynthesis. Results regarding CYP2E1 disposition may be useful for modeling the effects of CYP2E1 inducers and inhibitors. For prevention of CYP2E1-mediated bioactivation, depending on protoxicant disposition, a second DSF dose might be necessary to completely prevent toxicity.

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Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

One of the major reasons for studying chemical kinetics is to use measurements of the macroscopic properties of a system, COA of Formula: C7H4ClNO3, such as the rate of change in the concentration of reactants or products with time.In a article, mentioned the application of 1750-45-4, Name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, molecular formula is C7H4ClNO3

Laparoscopic Roux-en-Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates

There is a lack of information about the changes in drug pharmacokinetics and cytochrome P450 (CYP) metabolism after bariatric surgery. Here, we investigated the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery on pharmacokinetics of nine drugs given simultaneously which may reveal changes in the activities of the main CYPs. Eight obese subjects undergoing LRYGB received an oral cocktail containing nine drugs, substrates of various CYPs: melatonin (CYP1A2), nicotine (CYP2A6), bupropion (CYP2B6), repaglinide (CYP2C8), losartan (CYP2C9), omeprazole (CYP2C19/CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A). The 6-hours pharmacokinetic profiles in serum and urine of each drug or corresponding metabolite as well as their metabolic ratios were compared before surgery with those at a median 1?year later. LRYGB exerted variable effects on the pharmacokinetics of these drugs. The geometric mean AUC0-6 (90% confidence interval) of melatonin, bupropion, repaglinide, chlorzoxazone and midazolam after LRYGB was 27 (19%-41%), 54 (43%-67%), 44 (29%-66%), 160 (129%-197%) and 74 (62%-90%) of the pre-surgery values, respectively. The pharmacokinetics of losartan, omeprazole and dextromethorphan did not change in response to surgery. Nicotine was not detected in serum, while geometric mean of AUC0-6 of its metabolite, cotinine, increased by 1.7 times after surgery. There were 3.6- and 1.3-fold increases in the AUC ratios of 6-hydroxymelatonin/melatonin and hydroxybupropion/bupropion, respectively. The cocktail revealed multiple pharmacokinetic changes occurring after LRYGB with the greatest effects observed for CYP1A2, CYP2C8 and CYP2E1 substrates. Future studies should be focused on CYP1A2, CYP2A6, CYP2C8 and CYP2B6 to clarify the changes in activities of these enzymes after LRYGB.

Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. COA of Formula: C7H4ClNO3, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 1750-45-4, in my other articles.

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Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Related Products of 1750-45-4, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.1750-45-4, Name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, molecular formula is C7H4ClNO3. In a article£¬once mentioned of 1750-45-4

Expression and purification of human cytochrome P450

The invention provides a nucleic acid encoding a human cytochrome P450 2E1 comprising a 5′ terminal deletion of 63 nucleotides, thereby encoding methionine at the first codon position of the 5′ terminus, the codon ATG in the second codon position of the 5′ terminus, and silent adenine and thymine nucleotide substitutions in the 5′ region. The invention also provides a nucleic acid encoding a human cytochrome P450 2C10 comprising a 5′ terminal deletion of nucleotides 7 through 60, thereby encoding methionine at the first codon position and alanine at the second position of the 5′ terminus, and silent adenine and thymine nucleotide substitutions in the 5′ region. The present invention also provides a method of purifying a recombinant cytochrome P450 protein from a host cell culture comprising the steps of: a. fractionating the host cells to prepare their membranes; b. adding a non-ionic detergent in a concentration of between 0.8% to 2% (w/v) and in a detergent to protein ratio of between 4:1 to 10:1 to the membranes; c. adding an ionic detergent in a concentration of between 0.4% to 0.8% (w/v) and in a detergent to protein ratio of between 2:1 to 4:1 to the membranes; d. centrifuging the membrane detergent mixture to remove insoluble materials; and, e. purifying the protein in the following order: i) through a diethylaminoethyl-beaded column; ii) through a carboxymethyl-beaded column; and iii) through a hydroxylapatite column. The invention also provides a purified recombinant human cytochrome P450 1A1 which has retained its catalytic activity, such as catalyzing 7-ethoxyresorufin O-deethylation and benzo(a)pyrene 3-hydroxylation.

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Reference£º
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Electric Literature of 1750-45-4, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, and a compound is mentioned, 1750-45-4, 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one, introducing its new discovery.

Storage stability study of porcine hepatic and intestinal cytochrome P450 isoenzymes by use of a newly developed and fully validated highly sensitive HPLC-MS/MS method

Microsomes are an ideal medium to investigate cytochrome P450 (CYP450) enzyme-mediated drug metabolism. However, before microsomes are prepared, tissues can be stored for a long time. Studies about the stability of these enzymes in porcine hepatic and intestinal tissues upon storage are lacking. To be able to investigate CYP450 stability in microsomes prepared from these tissues, a highly sensitive and rapid HPLC-MS/MS method for the simultaneous determination of six CYP450 metabolites in incubation medium was developed and validated. The metabolites, paracetamol (CYP1A), 7-hydroxy-coumarin (CYP2A), 1-hydroxy-midazolam (CYP3A), 4-hydroxy-tolbutamide (CYP2C), dextrorphan (CYP2D), and 6-hydroxy-chlorzoxazone (CYP2E) were extracted with ethyl acetate at pH?1.0, followed by evaporation and separation on an Agilent Zorbax Eclipse Plus C18 column. The method was fully validated in a GLP-compliant laboratory according to European guidelines and was highly sensitive (LOQ = 0.25?2.5?ng/mL), selective, had good precision (RSD-within, 1.0?9.1%; RSD-between, 1.0?18.4%) and accuracy (within-run, 83.3?102%; between-run, 78.5?102%), and showed no relative signal suppression and enhancement. Consequently, this method was applied to study the stability of porcine hepatic and intestinal CYP450 isoenzymes when tissues were stored at ? 80?C. The results indicate that porcine CYP450 isoenzymes are stable in tissues at least up to 4?months when snap frozen and stored at ? 80?C. Moreover, the results indicate differences in porcine CYP450 stability compared to rat, rabbit, and fish CYP450, as observed by other research groups, hence stressing the importance to investigate the CYP450 stability of a specific species.

Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Electric Literature of 1750-45-4. In my other articles, you can also check out more blogs about 1750-45-4

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Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

In heterogeneous catalysis, the catalyst is in a different phase from the reactants. COA of Formula: C7H4ClNO3, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 1750-45-4, name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one. In an article£¬Which mentioned a new discovery about 1750-45-4

In vitro inhibitory effects of dihydromyricetin on human liver cytochrome p450 enzymes

Context: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods: The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs). Results: The results showed that DHM could inhibit the activity of CYP3A4, CYP2E1 and CYP2D6, with IC50 values of 14.75, 25.74 and 22.69 lM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that DHM was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2D6, with Ki values of 6.06, 9.24 and 10.52 lM, respectively. In addition, DHM is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 12.17/0.057 min1 lM1. Discussion and conclusion: The in vitro studies of DHM with CYP isoforms indicate that DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Further clinical studies are needed to evaluate the significance of this interaction.

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Reference£º
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem

Application of 1750-45-4, Chemistry is the experimental science by definition. We want to make observations to prove hypothesis. For this purpose, we perform experiments in the lab. 1750-45-4, Name is 5-Chloro-6-hydroxybenzo[d]oxazol-2(3H)-one,introducing its new discovery.

Selective inhibition of cytochrome P450 2D6 by sarpogrelate and its active metabolite, M-1, in human liver microsomes

The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6-mediated dextromethorphan O-demethylation with an IC 50 (Ki) value of 3.05 muM (1.24 muM), in a competitive manner. M-1 also markedly inhibited CYP2D6 activity; its inhibitory effect with an IC50 (Ki) value of 0.201 mu (0.120 muM) was more potent than that of sarpogrelate, and was similarly potent as quinidine (Ki, 0.129 muM), a well-known typical CYP2D6 inhibitor. In addition, sarpogrelate and M-1 strongly inhibited both CYP2D6-catalyzed bufuralol 19-hydroxylation and metoprolol a-hydroxylation activities. However, sarpogrelate and M-1 showed no apparent inhibition of the other following eight CYPs: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5. Upon 30-minute preincubation of human liver microsomes with sarpogrelate or M-1 in the presence of NADPH, no obvious shift in IC50 was observed in terms of inhibition of the nine CYP activities, suggesting that sarpogrelate and M-1 are not time-dependent inactivators. Sarpogrelate strongly inhibited the activity of CYP2D6 at clinically relevant concentrations in human liver microsomes. These observations suggest that sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug-drug interactions. Copyright

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Reference£º
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem