The in vitro metabolism of rivaroxaban, a novel, oral, direct issue Xa inhibitor for the prevention and remedy of thromboembolic issues, was investigated in a number of species, together with people. The target of this research was to elucidate metabolite constructions and establish the metabolic pathways to offer assist for in vivo security and medical research. [(14)C]Rivaroxaban was incubated with liver microsomes and hepatocytes of rats, canine, and people. The samples had been analyzed by high-performance liquid chromatography-(14)C-tandem mass spectroscopy, to generate metabolite profiles and suggest or affirm the constructions of the metabolites shaped. In vitro metabolite profiles confirmed no main variations between species.
The principle oxidative metabolic pathways recognized for all species had been hydroxylation on the morpholinone moiety (M-2, M-3, and M-8) and to a lesser extent on the oxazolidinone moiety (M-9). M-2 was the primary metabolite in all microsomal incubations. M-1, a morpholinone ring-opened product shaped by additional oxidation of M-2, was the primary metabolite in all hepatocyte incubations. Different pathways had been amide hydrolysis on the morpholinone ring (M-7) and the chlorothiophene amide moiety (M-13 and M-15). In hepatocytes, M-13 was readily conjugated with glycine, resulting in M-4. The metabolic destiny of unlabeled M-15 was investigated individually.
Incubations with human liver microsomes and hepatocytes confirmed that M-15 was first oxidized to the aldehyde intermediate M-16 and subsequently diminished to M-17 (alcohol) or oxidized to M-18 (carboxylic acid). No metabolism on the chlorothiophene moiety itself was discovered. Total, rivaroxaban confirmed no species variations in metabolism, with completely different unbiased metabolic pathways and no formation of reactive metabolites.
In vivo clearance predictions from in vitro assays require scaling elements to narrate the concentrations of hepatocytes or microsomal protein to the intact liver. 2. The goals had been to measure the variability in scaling elements for Wistar rat and beagle canine for which the literature is especially scarce and decide any intercourse variations. 3. Scaling elements had been decided by evaluating the cytochrome P450 (P450) content material in hepatocytes or microsomes in opposition to the P450 content material of recent liver homogenate. Using recent homogenate is really helpful as freezing can improve contamination and have an effect on the P450 assay.
Comparability of genistein metabolism in rats and people utilizing liver microsomes and hepatocytes.
Species variations and metabolism are probably the most essential elements in contemplating the results of genistein. The goal of this research was to have a greater information of the metabolic destiny of genistein in people as in contrast with rats. For this goal, radiolabeled genistein was incubated with human and rat liver microsomes and with cryopreserved hepatocytes from each species. Incubations had been carried out utilizing a variety of genistein concentrations to research the kinetics of formation of the metabolites. Metabolite profiling was obtained utilizing an HPLC system linked to a radioactivity detector.
Identification of the metabolites was primarily based on their retention occasions as in contrast with these of genuine requirements and on LC-MS (ESI-MS/MS) or NMR analyses. In each species, liver microsomes produced the identical three hydroxylated metabolites (8-OH, 6-OH and three’-OH-genistein) whereas cryopreserved hepatocytes produced the identical glucurono- and sulfo-conjugates (genistein 4′-O-sulfate 7-O-glucuronide, genistein 7-O-glucuronide, genistein 4′-O-glucuronide, genistein 7-O-sulfate and genistein 4′-O-sulfate). The speed of metabolism assorted with species. 3′-Hydroxygenistein was the predominant metabolite produced by rat liver microsomes, whereas in people 3′-hydroxy and 8-hydroxygenistein had been produced in the identical vary.
Metabolism of prazosin in rat, canine, and human liver microsomes and cryopreserved rat and human hepatocytes and characterization of metabolites by liquid chromatography/tandem mass spectrometry.
Prazosin (2-[4-(2-furanoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline) is an antihypertensive agent that was launched to the market in 1976. It has since established a wonderful security document. Nonetheless, in vitro metabolism of prazosin has not been investigated. This research describes the in vitro biotransformation of prazosin in liver microsomes from rats, canine, and people, in addition to rat and human cryopreserved hepatocytes and characterization of metabolites utilizing liquid chromatography/tandem mass spectrometry. The main in vivo biotransformation pathways reported beforehand in rats and canine embody demethylation, amide hydrolysis, and O-glucuronidation.
These metabolic pathways had been additionally confirmed in our research. As well as, a number of new metabolites had been characterised, together with a secure carbinolamine, an iminium species, and an enamine-all shaped by way of oxidation of the piperazine ring. Two ring-opened metabolites generated following oxidative cleavage of the furan ring had been additionally recognized. Utilizing semicarbazide hydrochloride as a trapping agent, an intermediate arising from opening of the furan ring was captured as a pyridazine product. Within the presence of glutathione, three glutathione conjugates had been detected in microsomal incubations, though they weren’t detected in cryopreserved hepatocytes.
Rat WS Seminal Vesicles Total RNA |
RR-407-WS |
Zyagen |
0.1mg |
EUR 160 |
Rat Seminal Vesicles Frozen Sections |
RF-407 |
Zyagen |
10 slides |
EUR 228 |
Human Seminal Vesicle Epithelial Cells |
ABC-TC3795 |
AcceGen |
1 vial |
Ask for price |
|
Description: Special edition cells are isolated from the tissue types described. Cells are sterility and virus tested. All tissues used for cell isolation are obtained under informed consent. Gentaur complies with the U.S. Health Insurance Portability and Accountability Act (HIPAA). Characterization standards for special edition cells have not been established. |
Rat Seminal Vesicles Paraffin Sections |
RP-407 |
Zyagen |
10 slides |
EUR 228 |
Mouse CD1 Seminal Vesicles Total RNA |
MR-407 |
Zyagen |
0.1mg |
EUR 160 |
Mouse C57 Seminal Vesicles Total RNA |
MR-407-C57 |
Zyagen |
0.1mg |
EUR 180 |
Human Seminal Vesicle Paraffin Sections |
HP-407 |
Zyagen |
10 slides |
EUR 319 |
Monkey Seminal Vesicles cDNA, Cynomolgus |
KD-407 |
Zyagen |
30 reactions |
EUR 316 |
Rat WS Seminal Vesicles Total Protein |
RT-407-WS |
Zyagen |
0.5mg |
EUR 153 |
Mouse Balbc Seminal Vesicles Total RNA |
MR-407-BLC |
Zyagen |
0.1mg |
EUR 180 |
Rat WS Seminal Vesicles Frozen Sections |
RF-407-WS |
Zyagen |
10 slides |
EUR 228 |
Mouse CD1 Seminal Vesicles Total Protein |
MT-407 |
Zyagen |
0.5mg |
EUR 153 |
Mouse BLC Seminal Vesicles Total Protein |
MT-407-BLC |
Zyagen |
0.5mg |
EUR 180 |
Mouse C57 Seminal Vesicles Total Protein |
MT-407-C57 |
Zyagen |
0.5mg |
EUR 180 |
Monkey Seminal Vesicles Total RNA, Rhesus |
UR-407 |
Zyagen |
0.1mg |
EUR 195 |
Rat WS Seminal Vesicles Paraffin Sections |
RP-407-WS |
Zyagen |
10 slides |
EUR 228 |
Rat Seminal Vesicles cDNA-Random Primer |
RD-407-RH |
Zyagen |
30 reactions |
EUR 243 |
Mouse CD1 Seminal Vesicles Frozen Sections |
MF-407 |
Zyagen |
10 slides |
EUR 228 |
Mouse BLC Seminal Vesicles Frozen Sections |
MF-407-BLC |
Zyagen |
10 slides |
EUR 253 |
Mouse C57 Seminal Vesicles Frozen Sections |
MF-407-C57 |
Zyagen |
10 slides |
EUR 253 |
Rat WS Seminal Vesicles cDNA-Oligo-dT |
RD-407-WS |
Zyagen |
30 reactions |
EUR 243 |
Monkey Seminal Vesicles Total RNA, Cynomolgus |
KR-407 |
Zyagen |
0.1mg |
EUR 195 |
Mouse CD1 Seminal Vesicles Paraffin Sections |
MP-407 |
Zyagen |
10 slides |
EUR 228 |
Mouse BLC Seminal Vesicles Paraffin Sections |
MP-407-BLC |
Zyagen |
10 slides |
EUR 253 |
Mouse C57 Seminal Vesicles Paraffin Sections |
MP-407-C57 |
Zyagen |
10 slides |
EUR 253 |
Monkey Seminal Vesicles Total Protein, Rhesus |
UT-407 |
Zyagen |
1mg |
EUR 176 |
Monkey Seminal Vesicle Frozen Sections, Rhesus |
UF407 |
Zyagen |
10 slides |
EUR 307 |
Monkey Seminal Vesicle Paraffin Sections, Rhesus |
UP-407 |
Zyagen |
10 slides |
EUR 280 |
Monkey Seminal Vesicle Frozen Sections, Cynomolgus |
KF407 |
Zyagen |
10 slides |
EUR 307 |
Mouse C57 Seminal Vesicles cDNA-Random Primer |
MD-407-C57-RH |
Zyagen |
30 reactions |
EUR 280 |
Mouse CD1 Seminal Vesicles cDNA-Random Primer |
MD-407-HR |
Zyagen |
30 reactions |
EUR 243 |
Human Seminal Plasma |
abx069938-500g |
Abbexa |
500 g |
EUR 1425 |
Monkey Seminal Vesicle Paraffin Sections, Cynomolgus |
KP-407 |
Zyagen |
10 slides |
EUR 280 |
Innovative Grade US Origin Bovine Seminal Vesicle |
IGBOSVF |
Innovative research |
each |
EUR 133 |
|
Description: Innovative Grade US Origin Bovine Seminal Vesicle |
Innovative Grade US Origin Bovine Seminal Vesicle |
IGBOSVP |
Innovative research |
each |
EUR 210 |
|
Description: Innovative Grade US Origin Bovine Seminal Vesicle |
Innovative Grade US Origin Bovine Seminal Vesicle |
IGBOSVS |
Innovative research |
each |
EUR 210 |
|
Description: Innovative Grade US Origin Bovine Seminal Vesicle |
Innovative Grade US Origin Bovine Seminal Vesicle |
IGBOSVZ |
Innovative research |
each |
EUR 133 |
|
Description: Innovative Grade US Origin Bovine Seminal Vesicle |
Total RNA - Human Adult Normal Tissue: Seminal Vesicle |
R1234214-10 |
Biochain |
10 ug |
EUR 329 |
Monkey Seminal Vesicles cDNA-Random Primer, Cynomolgus |
KD-407-RH |
Zyagen |
30 reactions |
EUR 316 |
Total Protein - Human Adult Normal Tissue: Seminal Vesicle |
P1234214 |
Biochain |
1 mg |
EUR 590 |
Rat Seminal vesicle secretory protein 2 (SVS2) ELISA Kit |
abx548030-96tests |
Abbexa |
96 tests |
EUR 687.5 |
Rat Seminal vesicle secretory protein 4 (SVS4) ELISA Kit |
abx548032-96tests |
Abbexa |
96 tests |
EUR 687.5 |
Rat Seminal vesicle secretory protein 5 (SVS5) ELISA Kit |
abx548034-96tests |
Abbexa |
96 tests |
EUR 687.5 |
Pooled Human Seminal Fluid |
IRHUSMF1ML |
Innovative research |
each |
EUR 247 |
|
Description: Pooled Human Seminal Fluid |
Pooled Human Seminal Fluid |
IRHUSMF5ML |
Innovative research |
each |
EUR 690 |
|
Description: Pooled Human Seminal Fluid |
Mouse Seminal vesicle secretory protein 6, Svs6 ELISA KIT |
ELI-41757m |
Lifescience Market |
96 Tests |
EUR 1038 |
Mouse Seminal vesicle secretory protein 4, Svs4 ELISA KIT |
ELI-23600m |
Lifescience Market |
96 Tests |
EUR 1038 |
Mouse Seminal vesicle secretory protein 5, Svs5 ELISA KIT |
ELI-19037m |
Lifescience Market |
96 Tests |
EUR 1038 |
Mouse Seminal vesicle secretory protein 4 (SVS4) ELISA Kit |
abx548031-96tests |
Abbexa |
96 tests |
EUR 687.5 |
Mouse Seminal vesicle secretory protein 5 (SVS5) ELISA Kit |
abx548033-96tests |
Abbexa |
96 tests |
EUR 687.5 |
Mouse Seminal vesicle secretory protein 6 (SVS6) ELISA Kit |
abx548035-96tests |
Abbexa |
96 tests |
EUR 687.5 |
Recombinant Mouse Seminal vesicle secretory protein 4 (Svs4) |
CSB-EP325982MO |
Cusabio |
10409 mg |
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Seminal Plasma, Human Protein |
abx069938-10ml |
Abbexa |
10 ml |
EUR 1111.2 |
|
Lactoferrin Human (Seminal Plasma) |
rAP-3527 |
Angio Proteomie |
Inquiry |
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Rat Secreted seminal- vesicle Ly- 6 protein 1, Sslp1 ELISA KIT |
ELI-42469r |
Lifescience Market |
96 Tests |
EUR 1063.2 |
Svs3a (untagged ORF) - Rat seminal vesicle secretion 3 (Svs3), (10 ug) |
RN202924 |
Origene Technologies GmbH |
10 µg |
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Lactoferrin (Seminal Plasma) Protein |
20-abx262658 |
Abbexa |
-
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|
|
Lactoferrin (Seminal Plasma) Protein |
abx262658-10mg |
Abbexa |
10 mg |
EUR 325 |
Lactoferrin (Seminal Plasma) Protein |
abx262658-25mg |
Abbexa |
25 mg |
EUR 6575 |
Lactoferrin (Seminal Plasma) Protein |
abx262658-5mg |
Abbexa |
5 mg |
EUR 225 |
Mouse Secreted seminal- vesicle Ly- 6 protein 1, Sslp1 ELISA KIT |
ELI-41041m |
Lifescience Market |
96 Tests |
EUR 1038 |
Bovine Secreted seminal- vesicle Ly- 6 protein 1, SSLP1 ELISA KI |
ELI-18704b |
Lifescience Market |
96 Tests |
EUR 1113.6 |
Porcine Secreted seminal- vesicle Ly- 6 protein 1, SSLP1 ELISA K |
ELI-41771p |
Lifescience Market |
96 Tests |
EUR 1113.6 |
Sval1 (untagged) - Mouse seminal vesicle antigen-like 1 (Sval1), (10ug) |
MC211200 |
Origene Technologies GmbH |
10 µg |
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Sval2 (untagged) - Mouse seminal vesicle antigen-like 2 (Sval2), (10ug) |
MC211975 |
Origene Technologies GmbH |
10 µg |
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Sval3 (untagged) - Mouse seminal vesicle antigen-like 3 (Sval3), (10ug) |
MC214842 |
Origene Technologies GmbH |
10 µg |
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Single Donor Human Seminal Fluid |
IRHUSSMF1ML |
Innovative research |
each |
EUR 247 |
|
Description: Single Donor Human Seminal Fluid |
Single Donor Human Seminal Fluid |
IRHUSSMF5ML |
Innovative research |
each |
EUR 689 |
|
Description: Single Donor Human Seminal Fluid |
Svs4 (untagged) - Mouse seminal vesicle secretory protein 4 (Svs4), (10ug) |
MC209484 |
Origene Technologies GmbH |
10 µg |
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Svs5 (untagged) - Mouse seminal vesicle secretory protein 5 (Svs5), (10ug) |
MC209485 |
Origene Technologies GmbH |
10 µg |
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Svs6 (untagged) - Mouse seminal vesicle secretory protein 6 (Svs6), (10ug) |
MC209486 |
Origene Technologies GmbH |
10 µg |
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Svs2 (untagged) - Mouse seminal vesicle secretory protein 2 (Svs2), (10ug) |
MC209952 |
Origene Technologies GmbH |
10 µg |
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Svs1 (untagged) - Mouse seminal vesicle secretory protein 1 (Svs1), (10ug) |
MC221903 |
Origene Technologies GmbH |
10 µg |
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Svs3a (untagged) - Mouse seminal vesicle secretory protein 3A (Svs3a), (10ug) |
MC210220 |
Origene Technologies GmbH |
10 µg |
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Svs3b (untagged) - Mouse seminal vesicle secretory protein 3B (Svs3b), (10ug) |
MC214561 |
Origene Technologies GmbH |
10 µg |
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Sval2 (untagged ORF) - Rat seminal vesicle antigen-like 2 (Sval2), (10 ug) |
RN209026 |
Origene Technologies GmbH |
10 µg |
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Sval1 (untagged ORF) - Rat seminal vesicle antigen-like 1 (Sval1), (10 ug) |
RN203350 |
Origene Technologies GmbH |
10 µg |
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Sval1 (GFP-tagged) - Mouse seminal vesicle antigen-like 1 (Sval1), (10ug) |
MG214120 |
Origene Technologies GmbH |
10 µg |
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Sval3 (GFP-tagged) - Mouse seminal vesicle antigen-like 3 (Sval3), (10ug) |
MG214355 |
Origene Technologies GmbH |
10 µg |
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Sval2 (GFP-tagged) - Mouse seminal vesicle antigen-like 2 (Sval2), (10ug) |
MG212653 |
Origene Technologies GmbH |
10 µg |
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Svs4 (untagged ORF) - Rat seminal vesicle secretory protein 4 (Svs4), (10 ug) |
RN206141 |
Origene Technologies GmbH |
10 µg |
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Svs5 (untagged ORF) - Rat seminal vesicle secretory protein 5 (Svs5), (10 ug) |
RN205622 |
Origene Technologies GmbH |
10 µg |
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Svs1 (untagged ORF) - Rat seminal vesicle secretory protein 1 (Svs1), (10 ug) |
RN202619 |
Origene Technologies GmbH |
10 µg |
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Svs6 (untagged ORF) - Rat seminal vesicle secretory protein 6 (Svs6), (10 ug) |
RN203700 |
Origene Technologies GmbH |
10 µg |
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Seminal Plasma Inhibin (67-94) (human) |
H-1602.0500 |
Bachem |
0.5mg |
EUR 400.8 |
Description: Sum Formula: C150H240N36O43S2; CAS# [96182-95-5] |
Seminal Plasma Inhibin (67-94) (human) |
H-1602.1000 |
Bachem |
1.0mg |
EUR 691.2 |
Description: Sum Formula: C150H240N36O43S2; CAS# [96182-95-5] |
Svs5 (GFP-tagged) - Mouse seminal vesicle secretory protein 5 (Svs5), (10ug) |
MG218264 |
Origene Technologies GmbH |
10 µg |
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Svs6 (GFP-tagged) - Mouse seminal vesicle secretory protein 6 (Svs6), (10ug) |
MG218311 |
Origene Technologies GmbH |
10 µg |
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Svs4 (GFP-tagged) - Mouse seminal vesicle secretory protein 4 (Svs4), (10ug) |
MG218371 |
Origene Technologies GmbH |
10 µg |
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Lenti ORF clone of Sva (mGFP-tagged) - Mouse seminal vesicle antigen (Sva) |
MR214416L4 |
Origene Technologies GmbH |
10 µg |
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Pate4 (untagged ORF) - Rat seminal vesicle secretory protein 7 (Svs7), (10 ug) |
RN205474 |
Origene Technologies GmbH |
10 µg |
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Svs5 (Myc-DDK-tagged) - Mouse seminal vesicle secretory protein 5 (Svs5) |
MR218264 |
Origene Technologies GmbH |
10 µg |
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Svs6 (Myc-DDK-tagged) - Mouse seminal vesicle secretory protein 6 (Svs6) |
MR218311 |
Origene Technologies GmbH |
10 µg |
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Svs4 (Myc-DDK-tagged) - Mouse seminal vesicle secretory protein 4 (Svs4) |
MR218371 |
Origene Technologies GmbH |
10 µg |
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Svs2 (Myc-DDK-tagged) - Mouse seminal vesicle secretory protein 2 (Svs2) |
MR215004 |
Origene Technologies GmbH |
10 µg |
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Svs3b (untagged ORF) - Rat seminal vesicle secretory protein 3B (Svs3b), (10 ug) |
RN209721 |
Origene Technologies GmbH |
10 µg |
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Svs3a (Myc-DDK-tagged) - Mouse seminal vesicle secretory protein 3A (Svs3a) |
MR212471 |
Origene Technologies GmbH |
10 µg |
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Svs3b (Myc-DDK-tagged) - Mouse seminal vesicle secretory protein 3B (Svs3b) |
MR214619 |
Origene Technologies GmbH |
10 µg |
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Svs3b (GFP-tagged) - Mouse seminal vesicle secretory protein 3B (Svs3b), (10ug) |
MG214619 |
Origene Technologies GmbH |
10 µg |
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Svs3a (GFP-tagged) - Mouse seminal vesicle secretory protein 3A (Svs3a), (10ug) |
MG212471 |
Origene Technologies GmbH |
10 µg |
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Svs3a (Myc-DDK-tagged ORF) - Rat seminal vesicle secretion 3 (Svs3), (10 ug) |
RR202924 |
Origene Technologies GmbH |
10 µg |
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Lenti ORF clone of Sva (Myc-DDK-tagged) - Mouse seminal vesicle antigen (Sva) |
MR214416L3 |
Origene Technologies GmbH |
10 µg |
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Bovine Seminal ribonuclease, SRN ELISA KIT |
ELI-40880b |
Lifescience Market |
96 Tests |
EUR 1113.6 |
Sval2 (Myc-DDK-tagged ORF) - Rat seminal vesicle antigen-like 2 (Sval2), (10 ug) |
RR209026 |
Origene Technologies GmbH |
10 µg |
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These information assist ring opening of the furan by way of a reactive gamma-keto-alpha,beta-unsaturated aldehyde intermediate. Within the presence of UDP-glucuronic acid, prazosin underwent conjugation to type an N-glucuronide not reported beforehand. Our in vitro investigations have revealed further metabolic transformations of prazosin and have proven the potential of prazosin to endure bioactivation by means of metabolism of the furan ring to a reactive intermediate.