CA2641325A1 - Methods for interfering with glucocorticoid induced gastric acid secretion - Google Patents
Methods for interfering with glucocorticoid induced gastric acid secretion Download PDFInfo
- Publication number
- CA2641325A1 CA2641325A1 CA002641325A CA2641325A CA2641325A1 CA 2641325 A1 CA2641325 A1 CA 2641325A1 CA 002641325 A CA002641325 A CA 002641325A CA 2641325 A CA2641325 A CA 2641325A CA 2641325 A1 CA2641325 A1 CA 2641325A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- hydroxy
- methoxy
- hydrazid
- benzyliden
- 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
- 238000000034 method Methods 0.000 title claims abstract description 40
- 239000003862 glucocorticoid Substances 0.000 title claims abstract description 25
- 230000027119 gastric acid secretion Effects 0.000 title claims abstract description 16
- 230000002452 interceptive effect Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 11
- 238000003745 diagnosis Methods 0.000 claims abstract description 11
- 230000001939 inductive effect Effects 0.000 claims abstract description 11
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 11
- 210000002966 serum Anatomy 0.000 claims abstract description 10
- 101000864800 Homo sapiens Serine/threonine-protein kinase Sgk1 Proteins 0.000 claims description 54
- 102100030070 Serine/threonine-protein kinase Sgk1 Human genes 0.000 claims description 53
- -1 3,4-Dichlor-phenyl Chemical group 0.000 claims description 32
- 101000864831 Homo sapiens Serine/threonine-protein kinase Sgk3 Proteins 0.000 claims description 28
- 102100030071 Serine/threonine-protein kinase Sgk3 Human genes 0.000 claims description 28
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 18
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 229920001184 polypeptide Polymers 0.000 claims description 16
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 15
- 230000014509 gene expression Effects 0.000 claims description 14
- 239000003112 inhibitor Substances 0.000 claims description 14
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 101000864806 Homo sapiens Serine/threonine-protein kinase Sgk2 Proteins 0.000 claims description 13
- 239000004202 carbamide Substances 0.000 claims description 11
- 239000002773 nucleotide Substances 0.000 claims description 11
- 125000003729 nucleotide group Chemical group 0.000 claims description 11
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 10
- 238000012216 screening Methods 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
- 230000026731 phosphorylation Effects 0.000 claims description 3
- 238000006366 phosphorylation reaction Methods 0.000 claims description 3
- IQKZROOLYSZNEJ-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(2,3,4,5,6-pentafluorophenyl)urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=C(F)C(F)=C(F)C(F)=C1F IQKZROOLYSZNEJ-UHFFFAOYSA-N 0.000 claims description 2
- MAABMJXGWVZVDA-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(2,3,4-trifluorophenyl)urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC=C(F)C(F)=C1F MAABMJXGWVZVDA-UHFFFAOYSA-N 0.000 claims description 2
- UQJOUZQWQLHFBD-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(2,4-difluorophenyl)urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC=C(F)C=C1F UQJOUZQWQLHFBD-UHFFFAOYSA-N 0.000 claims description 2
- RWWSBAFSWSCVMI-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(4-bromo-2,6-difluorophenyl)urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=C(F)C=C(Br)C=C1F RWWSBAFSWSCVMI-UHFFFAOYSA-N 0.000 claims description 2
- VOPLZUQRMLDRGL-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[2-[2-(dimethylamino)ethoxy]-4-fluorophenyl]urea Chemical compound CN(C)CCOC1=CC(F)=CC=C1NC(=O)NC1=CC=C(N2C3=NC=NC(N)=C3C(=O)C=C2)C=C1 VOPLZUQRMLDRGL-UHFFFAOYSA-N 0.000 claims description 2
- VVKPCIZJVWOWTP-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[2-chloro-5-[2-(diethylamino)ethoxy]phenyl]urea Chemical compound CCN(CC)CCOC1=CC=C(Cl)C(NC(=O)NC=2C=CC(=CC=2)N2C3=NC=NC(N)=C3C(=O)C=C2)=C1 VVKPCIZJVWOWTP-UHFFFAOYSA-N 0.000 claims description 2
- NKUBOVQYCDDOGW-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[2-fluoro-3-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC=CC(C(F)(F)F)=C1F NKUBOVQYCDDOGW-UHFFFAOYSA-N 0.000 claims description 2
- IVPXUSYAGFRVQE-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[2-fluoro-5-(2-piperidin-1-ylethoxy)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC(C(=CC=1)F)=CC=1OCCN1CCCCC1 IVPXUSYAGFRVQE-UHFFFAOYSA-N 0.000 claims description 2
- SMCZQWWBGCCPGR-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[2-fluoro-6-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=C(F)C=CC=C1C(F)(F)F SMCZQWWBGCCPGR-UHFFFAOYSA-N 0.000 claims description 2
- OOYNAKHTIZGWNY-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[3-chloro-2-piperidin-4-yloxy-5-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC(C(F)(F)F)=CC(Cl)=C1OC1CCNCC1 OOYNAKHTIZGWNY-UHFFFAOYSA-N 0.000 claims description 2
- JZKUTXXQAMHNLU-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[3-chloro-4-[2-(dimethylamino)ethoxy]phenyl]urea Chemical compound C1=C(Cl)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(N2C3=NC=NC(N)=C3C(=O)C=C2)C=C1 JZKUTXXQAMHNLU-UHFFFAOYSA-N 0.000 claims description 2
- FRFXBYMEIKEBQK-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[4-chloro-2-[2-(dimethylamino)ethoxy]phenyl]urea Chemical compound CN(C)CCOC1=CC(Cl)=CC=C1NC(=O)NC1=CC=C(N2C3=NC=NC(N)=C3C(=O)C=C2)C=C1 FRFXBYMEIKEBQK-UHFFFAOYSA-N 0.000 claims description 2
- GEZUVTIELGZOTM-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[4-chloro-2-piperidin-4-yloxy-5-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC(C(F)(F)F)=C(Cl)C=C1OC1CCNCC1 GEZUVTIELGZOTM-UHFFFAOYSA-N 0.000 claims description 2
- GQZWAUZYEGKPIB-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[4-chloro-3-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC=C(Cl)C(C(F)(F)F)=C1 GQZWAUZYEGKPIB-UHFFFAOYSA-N 0.000 claims description 2
- ZNCHDQIWUZRUSB-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[4-fluoro-3-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC=C(F)C(C(F)(F)F)=C1 ZNCHDQIWUZRUSB-UHFFFAOYSA-N 0.000 claims description 2
- PYTDJSCXRQHDGS-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[5-[2-(diethylamino)ethoxy]-2-fluorophenyl]urea Chemical compound CCN(CC)CCOC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)N2C3=NC=NC(N)=C3C(=O)C=C2)=C1 PYTDJSCXRQHDGS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000006193 alkinyl group Chemical group 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- RNRLEIGIUNHUDA-UHFFFAOYSA-N n-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-2,4-dichlorobenzamide Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C=C1Cl RNRLEIGIUNHUDA-UHFFFAOYSA-N 0.000 claims description 2
- NDEJVYMPHAQKJL-UHFFFAOYSA-N n-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-2-fluoro-5-(trifluoromethyl)benzamide Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)C1=CC(C(F)(F)F)=CC=C1F NDEJVYMPHAQKJL-UHFFFAOYSA-N 0.000 claims description 2
- RHVOGAZDHZDYNO-UHFFFAOYSA-N n-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-4-chloro-3-(trifluoromethyl)benzamide Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 RHVOGAZDHZDYNO-UHFFFAOYSA-N 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- SGGQZOONTMYDCO-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(2,4-dibromo-6-fluorophenyl)urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=C(F)C=C(Br)C=C1Br SGGQZOONTMYDCO-UHFFFAOYSA-N 0.000 claims 1
- DAUCFAKRDDFLRU-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)N2C3=NC=NC(N)=C3C(=O)C=C2)=C1 DAUCFAKRDDFLRU-UHFFFAOYSA-N 0.000 claims 1
- MNYXKYCDGKQGJW-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(2-piperidin-4-yloxyphenyl)urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1OC1CCNCC1 MNYXKYCDGKQGJW-UHFFFAOYSA-N 0.000 claims 1
- CKHCCGZEKOFGBE-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[2-[2-(diethylamino)ethoxy]-4-fluorophenyl]urea Chemical compound CCN(CC)CCOC1=CC(F)=CC=C1NC(=O)NC1=CC=C(N2C3=NC=NC(N)=C3C(=O)C=C2)C=C1 CKHCCGZEKOFGBE-UHFFFAOYSA-N 0.000 claims 1
- OWKPAZCWJGPSQU-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC(C(F)(F)F)=CC=C1F OWKPAZCWJGPSQU-UHFFFAOYSA-N 0.000 claims 1
- XNKQTNWFSAWEBR-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[3-chloro-4-(2-morpholin-4-ylethoxy)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC(C=C1Cl)=CC=C1OCCN1CCOCC1 XNKQTNWFSAWEBR-UHFFFAOYSA-N 0.000 claims 1
- RSGWOWXVHQYICD-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[3-chloro-4-[2-(diethylamino)ethoxy]phenyl]urea Chemical compound C1=C(Cl)C(OCCN(CC)CC)=CC=C1NC(=O)NC1=CC=C(N2C3=NC=NC(N)=C3C(=O)C=C2)C=C1 RSGWOWXVHQYICD-UHFFFAOYSA-N 0.000 claims 1
- WMERKKPANYWBAK-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[3-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC(F)=CC(C(F)(F)F)=C1 WMERKKPANYWBAK-UHFFFAOYSA-N 0.000 claims 1
- TZUPKKPJMPBSAS-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[4-fluoro-2-(2-morpholin-4-ylethoxy)phenyl]urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=CC=C(F)C=C1OCCN1CCOCC1 TZUPKKPJMPBSAS-UHFFFAOYSA-N 0.000 claims 1
- FEMIVGOPUOGDLB-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-[4-methyl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1NC(=O)NC1=CC=C(N2C3=NC=NC(N)=C3C(=O)C=C2)C=C1 FEMIVGOPUOGDLB-UHFFFAOYSA-N 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 claims 1
- 108060006633 protein kinase Proteins 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 239000000556 agonist Substances 0.000 abstract 1
- 230000001575 pathological effect Effects 0.000 abstract 1
- 101150082971 Sgk1 gene Proteins 0.000 description 34
- 241000699670 Mus sp. Species 0.000 description 29
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 18
- 229960003957 dexamethasone Drugs 0.000 description 18
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 18
- 230000028327 secretion Effects 0.000 description 16
- 230000002496 gastric effect Effects 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 210000002784 stomach Anatomy 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 10
- 230000001086 cytosolic effect Effects 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 208000025865 Ulcer Diseases 0.000 description 7
- 210000001711 oxyntic cell Anatomy 0.000 description 7
- 231100000397 ulcer Toxicity 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 230000004075 alteration Effects 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 210000004907 gland Anatomy 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 229940037128 systemic glucocorticoids Drugs 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 102400000921 Gastrin Human genes 0.000 description 5
- 108010052343 Gastrins Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 210000004211 gastric acid Anatomy 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
- 229960000381 omeprazole Drugs 0.000 description 5
- 108091006146 Channels Proteins 0.000 description 4
- 108010011185 KCNQ1 Potassium Channel Proteins 0.000 description 4
- 229940126213 SGK1 inhibitor Drugs 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 230000004224 protection Effects 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101000974726 Homo sapiens Potassium voltage-gated channel subfamily E member 1 Proteins 0.000 description 3
- 101710122864 Major tegument protein Proteins 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 3
- 101710148592 PTS system fructose-like EIIA component Proteins 0.000 description 3
- 101710169713 PTS system fructose-specific EIIA component Proteins 0.000 description 3
- 102100022755 Potassium voltage-gated channel subfamily E member 1 Human genes 0.000 description 3
- 102100037444 Potassium voltage-gated channel subfamily KQT member 1 Human genes 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 108010083644 Ribonucleases Proteins 0.000 description 3
- 102000006382 Ribonucleases Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 101710199973 Tail tube protein Proteins 0.000 description 3
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 229910052796 boron Inorganic materials 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 230000005754 cellular signaling Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 3
- 210000001198 duodenum Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- DANUORFCFTYTSZ-UHFFFAOYSA-N epinigericin Natural products O1C2(C(CC(C)(O2)C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)C)C(C)C(OC)CC1CC1CCC(C)C(C(C)C(O)=O)O1 DANUORFCFTYTSZ-UHFFFAOYSA-N 0.000 description 3
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 3
- 210000001156 gastric mucosa Anatomy 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- DANUORFCFTYTSZ-BIBFWWMMSA-N nigericin Chemical compound C([C@@H]1C[C@H]([C@H]([C@]2([C@@H](C[C@](C)(O2)C2O[C@@](C)(CC2)C2[C@H](CC(O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C)O1)C)OC)[C@H]1CC[C@H](C)C([C@@H](C)C(O)=O)O1 DANUORFCFTYTSZ-BIBFWWMMSA-N 0.000 description 3
- 230000020477 pH reduction Effects 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 150000003180 prostaglandins Chemical class 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 3
- 239000008399 tap water Substances 0.000 description 3
- 235000020679 tap water Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
- IKTHMQYJOWTSJO-UHFFFAOYSA-N 4-Acetyl-6-tert-butyl-1,1-dimethylindane Chemical compound CC(=O)C1=CC(C(C)(C)C)=CC2=C1CCC2(C)C IKTHMQYJOWTSJO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108700039887 Essential Genes Proteins 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- HRNLUBSXIHFDHP-UHFFFAOYSA-N N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC1=NC=CC(C=2C=NC=CC=2)=N1 HRNLUBSXIHFDHP-UHFFFAOYSA-N 0.000 description 2
- 229910020700 Na3VO4 Inorganic materials 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 description 2
- 108010083204 Proton Pumps Proteins 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 239000012891 Ringer solution Substances 0.000 description 2
- 101150067005 Sgk3 gene Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001839 endoscopy Methods 0.000 description 2
- 210000003722 extracellular fluid Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000011880 melting curve analysis Methods 0.000 description 2
- 239000002395 mineralocorticoid Substances 0.000 description 2
- 235000019799 monosodium phosphate Nutrition 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 210000000287 oocyte Anatomy 0.000 description 2
- 230000021962 pH elevation Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000017619 regulation of gastric acid secretion Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- PTWIDYOHXRVLNM-UHFFFAOYSA-N 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8-yl)phenyl]-3-(2,6-difluorophenyl)urea Chemical compound C1=CC(=O)C=2C(N)=NC=NC=2N1C(C=C1)=CC=C1NC(=O)NC1=C(F)C=CC=C1F PTWIDYOHXRVLNM-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010029240 Cell-Tak Proteins 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- SRUWWOSWHXIIIA-UKPGNTDSSA-N Cyanoginosin Chemical compound N1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](C)[C@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C(=C)N(C)C(=O)CC[C@H](C(O)=O)N(C)C(=O)[C@@H](C)[C@@H]1\C=C\C(\C)=C\[C@H](C)[C@@H](O)CC1=CC=CC=C1 SRUWWOSWHXIIIA-UKPGNTDSSA-N 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102100035493 E3 ubiquitin-protein ligase NEDD4-like Human genes 0.000 description 1
- 101710155393 E3 ubiquitin-protein ligase NEDD4-like 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
- 238000002965 ELISA Methods 0.000 description 1
- 102100031563 Excitatory amino acid transporter 1 Human genes 0.000 description 1
- 102000018711 Facilitative Glucose Transport Proteins Human genes 0.000 description 1
- 210000000712 G cell Anatomy 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 102100033417 Glucocorticoid receptor Human genes 0.000 description 1
- 108091052347 Glucose transporter family Proteins 0.000 description 1
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 1
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- 101000944272 Homo sapiens ATP-sensitive inward rectifier potassium channel 1 Proteins 0.000 description 1
- 101000694017 Homo sapiens Sodium channel protein type 5 subunit alpha Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 201000002980 Hyperparathyroidism Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000015580 Increased body weight Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108700025784 N-myc downstream-regulated gene 1 Proteins 0.000 description 1
- 101150097297 Nedd4 gene Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010051741 Pancreas infection Diseases 0.000 description 1
- 108010047320 Pepsinogen A Proteins 0.000 description 1
- 102000015176 Proton-Translocating ATPases Human genes 0.000 description 1
- 108010039518 Proton-Translocating ATPases Proteins 0.000 description 1
- 108091006277 SLC5A1 Proteins 0.000 description 1
- 108091006649 SLC9A3 Proteins 0.000 description 1
- CGNLCCVKSWNSDG-UHFFFAOYSA-N SYBR Green I Chemical compound CN(C)CCCN(CCC)C1=CC(C=C2N(C3=CC=CC=C3S2)C)=C2C=CC=CC2=[N+]1C1=CC=CC=C1 CGNLCCVKSWNSDG-UHFFFAOYSA-N 0.000 description 1
- 102000058090 Sodium-Glucose Transporter 1 Human genes 0.000 description 1
- 102100030375 Sodium/hydrogen exchanger 3 Human genes 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 102000003734 Voltage-Gated Potassium Channels Human genes 0.000 description 1
- 108090000013 Voltage-Gated Potassium Channels Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- NTECHUXHORNEGZ-UHFFFAOYSA-N acetyloxymethyl 3',6'-bis(acetyloxymethoxy)-2',7'-bis[3-(acetyloxymethoxy)-3-oxopropyl]-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-carboxylate Chemical compound O1C(=O)C2=CC(C(=O)OCOC(C)=O)=CC=C2C21C1=CC(CCC(=O)OCOC(C)=O)=C(OCOC(C)=O)C=C1OC1=C2C=C(CCC(=O)OCOC(=O)C)C(OCOC(C)=O)=C1 NTECHUXHORNEGZ-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000009858 acid secretion Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 210000001109 blastomere Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012240 conditional targeting Methods 0.000 description 1
- 108010024505 crosstide peptide Proteins 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960004833 dexamethasone phosphate Drugs 0.000 description 1
- VQODGRNSFPNSQE-CXSFZGCWSA-N dexamethasone phosphate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP(O)(O)=O)(O)[C@@]1(C)C[C@@H]2O VQODGRNSFPNSQE-CXSFZGCWSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000009454 functional inhibition Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000002575 gastroscopy Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 210000004937 luminal membrane Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 238000001531 micro-dissection Methods 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 108010067094 microcystin Proteins 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229960004872 nizatidine Drugs 0.000 description 1
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229940037129 plain mineralocorticoids for systemic use Drugs 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 108010022404 serum-glucocorticoid regulated kinase Proteins 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 210000002325 somatostatin-secreting cell Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 108010030908 system N protein 1 Proteins 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
- C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/06—Gastro-intestinal diseases
- G01N2800/062—Gastritis or peptic ulcer disease
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Urology & Nephrology (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06001934.6 | 2006-01-31 | ||
EP06001934 | 2006-01-31 | ||
PCT/EP2007/000350 WO2007087985A1 (en) | 2006-01-31 | 2007-01-17 | Methods for interfering with glucocorticoid induced gastric acid secretion |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2641325A1 true CA2641325A1 (en) | 2007-08-09 |
Family
ID=38006823
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002641325A Abandoned CA2641325A1 (en) | 2006-01-31 | 2007-01-17 | Methods for interfering with glucocorticoid induced gastric acid secretion |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1979747A1 (de) |
JP (1) | JP2009531020A (de) |
AR (1) | AR059258A1 (de) |
AU (1) | AU2007211655A1 (de) |
CA (1) | CA2641325A1 (de) |
IL (1) | IL193081A0 (de) |
WO (1) | WO2007087985A1 (de) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20210008193A (ko) * | 2019-07-10 | 2021-01-21 | 한양대학교 산학협력단 | 염증성 신경 질환의 치료제로서 Sgk1 저해제의 용도 |
WO2022093780A1 (en) * | 2020-10-26 | 2022-05-05 | University Of North Dakota | Use of small molecule fak activators to promote mucosal healing |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10346913A1 (de) * | 2003-10-09 | 2005-05-04 | Merck Patent Gmbh | Acylhydrazonderivate |
WO2005084651A2 (en) * | 2004-03-08 | 2005-09-15 | Merck Patent Gmbh | Methods for altering insulin secretion |
CA2559141A1 (en) * | 2004-03-11 | 2005-10-13 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Methods for interfering with fibrosis |
RU2006135654A (ru) * | 2004-03-11 | 2008-09-10 | Мерк Патент ГмбХ (DE) | Способы модуляции глутаматных рецепторов для лечения нейропсихиатрических расстройств, включающие применение модуляторов сывороточных и индуцируемых глюкокортикоидами киназ |
US20090136920A1 (en) * | 2004-04-30 | 2009-05-28 | Stefan Golz | Diagnostics and therapeutics for diseases associated with serum/glucocorticoid regulated kinase 1 (sgk1) |
-
2007
- 2007-01-17 AU AU2007211655A patent/AU2007211655A1/en not_active Abandoned
- 2007-01-17 JP JP2008552709A patent/JP2009531020A/ja active Pending
- 2007-01-17 EP EP07702807A patent/EP1979747A1/de not_active Withdrawn
- 2007-01-17 WO PCT/EP2007/000350 patent/WO2007087985A1/en active Application Filing
- 2007-01-17 CA CA002641325A patent/CA2641325A1/en not_active Abandoned
- 2007-01-31 AR ARP070100405A patent/AR059258A1/es unknown
-
2008
- 2008-07-27 IL IL193081A patent/IL193081A0/en unknown
Also Published As
Publication number | Publication date |
---|---|
WO2007087985A1 (en) | 2007-08-09 |
AU2007211655A1 (en) | 2007-08-09 |
EP1979747A1 (de) | 2008-10-15 |
JP2009531020A (ja) | 2009-09-03 |
IL193081A0 (en) | 2009-02-11 |
AR059258A1 (es) | 2008-03-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Bouchard | Genetics of obesity: what we have learned over decades of research | |
Gorsic et al. | Functional genetic variation in the anti-Müllerian hormone pathway in women with polycystic ovary syndrome | |
Huang et al. | Blunted hypertensive effect of combined fructose and high-salt diet in gene-targeted mice lacking functional serum-and glucocorticoid-inducible kinase SGK1 | |
Turan et al. | GNAS spectrum of disorders | |
Skov et al. | Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome | |
Valverde et al. | Molecular mechanisms of insulin resistance in IRS-2-deficient hepatocytes | |
Hirashima et al. | Insulin down-regulates insulin receptor substrate-2 expression through the phosphatidylinositol 3-kinase/Akt pathway | |
Hwang et al. | A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study | |
Schwab et al. | Association of SGK1 gene polymorphisms with type 2 diabetes | |
Vangipurapu et al. | Association of indices of liver and adipocyte insulin resistance with 19 confirmed susceptibility loci for type 2 diabetes in 6,733 non-diabetic Finnish men | |
EP2344671B1 (de) | Ngal als biomarker zur aktivierung von mineralocorticoid-rezeptoren | |
Grahammer et al. | Intestinal function of gene-targeted mice lacking serum-and glucocorticoid-inducible kinase 1 | |
Minn et al. | Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein | |
Wang et al. | Whole-exome sequencing reveals SALL4 variants in premature ovarian insufficiency: an update on genotype–phenotype correlations | |
Ghanaat-Pour et al. | Global expression profiling of glucose-regulated genes in pancreatic islets of spontaneously diabetic Goto-Kakizaki rats | |
Pecak et al. | Multiomics data triangulation for asthma candidate biomarkers and precision medicine | |
Chatterjee et al. | Transporter activity changes in nonalcoholic steatohepatitis: assessment with plasma coproporphyrin I and III | |
Stork et al. | Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism | |
CA2641325A1 (en) | Methods for interfering with glucocorticoid induced gastric acid secretion | |
US20060014178A1 (en) | Use of Mrf-2 for screening and therapies | |
Sandu et al. | Role of the serum and glucocorticoid inducible kinase SGK1 in glucocorticoid stimulation of gastric acid secretion | |
WO2005108613A9 (en) | Human type ii diabetes gene-kv channel-interacting protein (kchip1) located on chromosome 5 | |
Müller et al. | SNP dependent modulation of circulating miRNAs from the miR25/93/106 cluster in patients undergoing weight loss | |
Osterhoff et al. | Identification of a functional protein kinase Cβ promoter polymorphism in humans related to insulin resistance | |
López-Alarcón et al. | PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Discontinued |