CA2352523A1 - Method of screening candidate compounds for susceptibility to oxidative metabolism - Google Patents
Method of screening candidate compounds for susceptibility to oxidative metabolism Download PDFInfo
- Publication number
- CA2352523A1 CA2352523A1 CA002352523A CA2352523A CA2352523A1 CA 2352523 A1 CA2352523 A1 CA 2352523A1 CA 002352523 A CA002352523 A CA 002352523A CA 2352523 A CA2352523 A CA 2352523A CA 2352523 A1 CA2352523 A1 CA 2352523A1
- Authority
- CA
- Canada
- Prior art keywords
- enzyme
- metabolism
- testosterone
- cyp3a4
- dcf
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 116
- 238000000034 method Methods 0.000 title claims abstract description 85
- 238000012216 screening Methods 0.000 title claims abstract description 22
- 230000004783 oxidative metabolism Effects 0.000 title description 10
- 230000004060 metabolic process Effects 0.000 claims abstract description 84
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 claims abstract description 68
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 claims abstract description 68
- 102000004190 Enzymes Human genes 0.000 claims abstract description 52
- 108090000790 Enzymes Proteins 0.000 claims abstract description 52
- 230000002503 metabolic effect Effects 0.000 claims abstract description 29
- 239000002243 precursor Substances 0.000 claims abstract description 25
- 238000007086 side reaction Methods 0.000 claims abstract description 19
- 239000013626 chemical specie Substances 0.000 claims abstract description 14
- 238000001514 detection method Methods 0.000 claims abstract description 5
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 claims description 78
- 102100039205 Cytochrome P450 3A4 Human genes 0.000 claims description 75
- 108010074922 Cytochrome P-450 CYP1A2 Proteins 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 239000003642 reactive oxygen metabolite Substances 0.000 claims description 17
- 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 claims description 8
- 102100029358 Cytochrome P450 2C9 Human genes 0.000 claims description 8
- 108010026925 Cytochrome P-450 CYP2C19 Proteins 0.000 claims description 7
- 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 claims description 7
- 102100029363 Cytochrome P450 2C19 Human genes 0.000 claims description 7
- 102100021704 Cytochrome P450 2D6 Human genes 0.000 claims description 6
- 108010093894 Xanthine oxidase Proteins 0.000 claims description 3
- 102100033220 Xanthine oxidase Human genes 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 102100026533 Cytochrome P450 1A2 Human genes 0.000 claims 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 207
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- 230000001404 mediated effect Effects 0.000 description 64
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 45
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 40
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 40
- 239000000758 substrate Substances 0.000 description 39
- 238000011534 incubation Methods 0.000 description 37
- 102000008144 Cytochrome P-450 CYP1A2 Human genes 0.000 description 27
- CRCWUBLTFGOMDD-UHFFFAOYSA-N 7-ethoxyresorufin Chemical compound C1=CC(=O)C=C2OC3=CC(OCC)=CC=C3N=C21 CRCWUBLTFGOMDD-UHFFFAOYSA-N 0.000 description 25
- 239000003814 drug Substances 0.000 description 24
- 229960003893 phenacetin Drugs 0.000 description 23
- 229940079593 drug Drugs 0.000 description 20
- 238000005259 measurement Methods 0.000 description 20
- XNZRYTITWLGTJS-UHFFFAOYSA-N 7-phenylmethoxyphenoxazin-3-one Chemical compound C1=C2OC3=CC(=O)C=CC3=NC2=CC=C1OCC1=CC=CC=C1 XNZRYTITWLGTJS-UHFFFAOYSA-N 0.000 description 19
- 239000002207 metabolite Substances 0.000 description 19
- HSSLDCABUXLXKM-UHFFFAOYSA-N resorufin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3N=C21 HSSLDCABUXLXKM-UHFFFAOYSA-N 0.000 description 18
- 238000003556 assay Methods 0.000 description 17
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 15
- 229960001985 dextromethorphan Drugs 0.000 description 15
- 229960004125 ketoconazole Drugs 0.000 description 15
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 230000003647 oxidation Effects 0.000 description 13
- 238000007254 oxidation reaction Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 11
- KGQZGCIVHYLPBH-UHFFFAOYSA-N Furafylline Chemical compound O=C1N(C)C(=O)C=2NC(C)=NC=2N1CC1=CC=CO1 KGQZGCIVHYLPBH-UHFFFAOYSA-N 0.000 description 10
- 108010044467 Isoenzymes Proteins 0.000 description 10
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- 230000005284 excitation Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
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- 108090000623 proteins and genes Proteins 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000002798 spectrophotometry method Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
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- 239000000126 substance Substances 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
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- 239000000186 progesterone Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000010517 secondary reaction Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- -1 CYP3A40R Chemical compound 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000012203 high throughput assay Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
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- 230000002829 reductive effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 150000003515 testosterones Chemical class 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 231100000357 carcinogen Toxicity 0.000 description 2
- 239000003183 carcinogenic agent Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000000295 emission spectrum Methods 0.000 description 2
- 239000003344 environmental pollutant Substances 0.000 description 2
- 238000000695 excitation spectrum Methods 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000003269 fluorescent indicator Substances 0.000 description 2
- 238000013537 high throughput screening Methods 0.000 description 2
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000013383 initial experiment Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000037323 metabolic rate Effects 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000002676 xenobiotic agent Substances 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- BFZHCUBIASXHPK-ODYOLWGQSA-N 11a-Hydroxyprogesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC(C(=O)C)[C@@]1(C)C[C@H]2O BFZHCUBIASXHPK-ODYOLWGQSA-N 0.000 description 1
- UOMQUZPKALKDCA-UHFFFAOYSA-K 2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxymethyl)amino]acetate;iron(3+) Chemical compound [Fe+3].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UOMQUZPKALKDCA-UHFFFAOYSA-K 0.000 description 1
- RPHLQSHHTJORHI-UHFFFAOYSA-N Adrenochrome Chemical compound O=C1C(=O)C=C2N(C)CC(O)C2=C1 RPHLQSHHTJORHI-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101150051438 CYP gene Proteins 0.000 description 1
- 101100497948 Caenorhabditis elegans cyn-1 gene Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 101710142428 Cytochrome P450 2C19 Proteins 0.000 description 1
- 101710101953 Cytochrome P450 2C9 Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 108010045510 NADPH-Ferrihemoprotein Reductase Proteins 0.000 description 1
- 101150053185 P450 gene Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000529895 Stercorarius Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- YXKTVDFXDRQTKV-HNNXBMFYSA-N benzphetamine Chemical compound C([C@H](C)N(C)CC=1C=CC=CC=1)C1=CC=CC=C1 YXKTVDFXDRQTKV-HNNXBMFYSA-N 0.000 description 1
- 229960002837 benzphetamine Drugs 0.000 description 1
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- 229940000406 drug candidate Drugs 0.000 description 1
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- 230000036267 drug metabolism Effects 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 239000003256 environmental substance Substances 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000012215 gene cloning Methods 0.000 description 1
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 1
- 229960002456 hexobarbital Drugs 0.000 description 1
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- 230000002452 interceptive effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
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- 238000004020 luminiscence type Methods 0.000 description 1
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- 230000007246 mechanism Effects 0.000 description 1
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- 239000003068 molecular probe Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/205,762 US6312917B1 (en) | 1998-12-04 | 1998-12-04 | Method of screening candidate compounds for susceptibility to oxidative metabolism |
| US09/205,762 | 1998-12-04 | ||
| PCT/US1999/027130 WO2000034506A2 (en) | 1998-12-04 | 1999-11-15 | Method of screening candidate compounds for susceptibility to oxidative metabolism |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2352523A1 true CA2352523A1 (en) | 2000-06-15 |
Family
ID=22763550
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002352523A Abandoned CA2352523A1 (en) | 1998-12-04 | 1999-11-15 | Method of screening candidate compounds for susceptibility to oxidative metabolism |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6312917B1 (https=) |
| EP (1) | EP1135521B1 (https=) |
| JP (1) | JP2002531138A (https=) |
| KR (1) | KR20010093140A (https=) |
| AT (1) | ATE317914T1 (https=) |
| AU (1) | AU774229B2 (https=) |
| BR (1) | BR9916458A (https=) |
| CA (1) | CA2352523A1 (https=) |
| DE (1) | DE69929900T2 (https=) |
| MX (1) | MXPA01005528A (https=) |
| NZ (1) | NZ512217A (https=) |
| WO (1) | WO2000034506A2 (https=) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6632630B2 (en) * | 2000-03-29 | 2003-10-14 | Aclara Biosciences, Inc. | Monooxygenase assays |
| US20050159901A1 (en) * | 2001-04-02 | 2005-07-21 | Astex Technology Limited | Crystal structure of cytochrome P450 |
| US20050032119A1 (en) * | 2001-04-02 | 2005-02-10 | Astex Technology Ltd. | Crystal structure of cytochrome P450 |
| US7148046B2 (en) * | 2001-04-02 | 2006-12-12 | Astex Therapeutics Limited | Crystal structure of cytochrome P450 |
| US20070179716A1 (en) * | 2001-04-02 | 2007-08-02 | Astex Therapeutics Limited | Crystal structure of cytochrome P450 3A4 and uses thereof |
| AU2002365070A1 (en) * | 2001-08-03 | 2003-06-30 | Diversa Corporation | P450 enzymes, nucleic acids encoding them and methods of making and using them |
| DE60214869T2 (de) * | 2001-10-25 | 2007-04-12 | Astex Technology Ltd., Cambridge | Cytochrome p450 2c9 kristalle, strukturen und dessen verwendung |
| US20040053383A1 (en) * | 2001-10-25 | 2004-03-18 | Astex Technology Ltd. | Crystals of cytochrome P450 2C9, structures thereof and their use |
| US20040096874A1 (en) * | 2002-04-11 | 2004-05-20 | Third Wave Technologies, Inc. | Characterization of CYP 2D6 genotypes |
| US20050164341A1 (en) * | 2002-05-30 | 2005-07-28 | Jose Cosme | Methods of purification of cytochrome p450 proteins and of their crystallizing |
| GB0216203D0 (en) * | 2002-07-12 | 2002-08-21 | Imp Cancer Res Tech | Mondulation of cytochrome P450 reductase activity |
| EP1546162B1 (en) | 2002-09-20 | 2011-06-22 | Promega Corporation | Luminescence-based methods and probes for measuring cytochrome p450 activity |
| WO2004038015A1 (en) * | 2002-10-25 | 2004-05-06 | Astex Technology Limited | Crystal structure of cytochrome p450 3a4 and its use |
| US20040219602A1 (en) * | 2003-03-01 | 2004-11-04 | Symyx Technologies, Inc. | Evaluating effects of exposure conditions on drug samples over time |
| WO2005098025A2 (en) * | 2004-04-05 | 2005-10-20 | The University Of North Carolina At Chapel Hill | High throughput reactive oxygen species-based cytochrome p450 inhibition assay |
| US20060046278A1 (en) * | 2004-08-26 | 2006-03-02 | Qualyst, Inc. | Methods and kits for determining metabolic stability of compounds |
| US20060223135A1 (en) * | 2005-04-05 | 2006-10-05 | The University Of North Carolina At Chapel Hill | High throughput reactive oxygen species-based cytochrome P450 inhibition assay |
| EP2272972A1 (en) | 2005-05-31 | 2011-01-12 | Promega Corporation | Luminogenic and fluorogenic compounds and methods to detect molecules or conditions |
| US20090318561A1 (en) * | 2008-06-23 | 2009-12-24 | Mutual Pharmaceutical Company, Inc. | Colchicine products, method of manufacture, and methods of use |
| US8288559B2 (en) | 2008-08-18 | 2012-10-16 | Promega Corporation | Luminogenic compounds and methods to detect cytochrome P450 3A enzymes |
| US9790537B2 (en) | 2014-01-29 | 2017-10-17 | Promega Corporation | Quinone-masked probes as labeling reagents for cell uptake measurements |
| WO2018118897A1 (en) * | 2016-12-19 | 2018-06-28 | Dice Molecules Sv, Llc | Methods of estimating metabolic stability of tagged combinatorial library compounds |
| WO2024223797A1 (en) | 2023-04-28 | 2024-10-31 | Institut National de la Santé et de la Recherche Médicale | Use of cyp3a4 inhibitors for the treatment of hepatitis d virus (hdv) infections |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4341868A (en) * | 1978-08-18 | 1982-07-27 | Kyowa Hakko Kogyo Co., Ltd. | Method and test composition for the determination of the substrate for xanthine oxidase |
| WO1980000454A1 (fr) | 1978-08-18 | 1980-03-20 | Kyowa Hakko Kogyo Kk | Methode de mesure d'un substrat de xanthine oxydase et composition pour sa determination |
| JP2515551B2 (ja) * | 1987-06-08 | 1996-07-10 | 和光純薬工業株式会社 | 新規な過酸化水素の定量方法 |
| US5413915A (en) | 1988-07-12 | 1995-05-09 | Resource Technologies Group, Inc. | Method and sensor for detecting toxic chemical exposure effects and metabolic activation of carcinogenic chemical agents |
| AU1970897A (en) | 1996-04-15 | 1997-11-07 | Fox Chase Cancer Center | Assays for detection of purine metabolites |
| GB9821932D0 (en) | 1998-10-09 | 1998-12-02 | Univ Leicester | Cytochrome P450 electrochemical system |
-
1998
- 1998-12-04 US US09/205,762 patent/US6312917B1/en not_active Expired - Fee Related
-
1999
- 1999-11-15 JP JP2000586939A patent/JP2002531138A/ja active Pending
- 1999-11-15 EP EP99957569A patent/EP1135521B1/en not_active Expired - Lifetime
- 1999-11-15 NZ NZ512217A patent/NZ512217A/en not_active IP Right Cessation
- 1999-11-15 BR BR9916458-2A patent/BR9916458A/pt not_active Application Discontinuation
- 1999-11-15 WO PCT/US1999/027130 patent/WO2000034506A2/en not_active Ceased
- 1999-11-15 KR KR1020017006953A patent/KR20010093140A/ko not_active Ceased
- 1999-11-15 AT AT99957569T patent/ATE317914T1/de not_active IP Right Cessation
- 1999-11-15 AU AU15250/00A patent/AU774229B2/en not_active Ceased
- 1999-11-15 MX MXPA01005528A patent/MXPA01005528A/es not_active IP Right Cessation
- 1999-11-15 DE DE69929900T patent/DE69929900T2/de not_active Expired - Fee Related
- 1999-11-15 CA CA002352523A patent/CA2352523A1/en not_active Abandoned
-
2001
- 2001-11-05 US US09/993,842 patent/US20020058295A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1135521A2 (en) | 2001-09-26 |
| ATE317914T1 (de) | 2006-03-15 |
| EP1135521B1 (en) | 2006-02-15 |
| WO2000034506A3 (en) | 2000-11-23 |
| KR20010093140A (ko) | 2001-10-27 |
| WO2000034506A2 (en) | 2000-06-15 |
| NZ512217A (en) | 2002-03-28 |
| AU1525000A (en) | 2000-06-26 |
| AU774229B2 (en) | 2004-06-17 |
| MXPA01005528A (es) | 2002-04-24 |
| DE69929900T2 (de) | 2006-08-17 |
| US6312917B1 (en) | 2001-11-06 |
| BR9916458A (pt) | 2001-09-04 |
| US20020058295A1 (en) | 2002-05-16 |
| JP2002531138A (ja) | 2002-09-24 |
| DE69929900D1 (de) | 2006-04-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |