EA007029B1 - Стимуляция срт-1 как средство уменьшения веса - Google Patents
Стимуляция срт-1 как средство уменьшения веса Download PDFInfo
- Publication number
- EA007029B1 EA007029B1 EA200401052A EA200401052A EA007029B1 EA 007029 B1 EA007029 B1 EA 007029B1 EA 200401052 A EA200401052 A EA 200401052A EA 200401052 A EA200401052 A EA 200401052A EA 007029 B1 EA007029 B1 EA 007029B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- cpt
- activity
- agent
- malonyl coenzyme
- fatty acid
- Prior art date
Links
- 101150073133 Cpt1a gene Proteins 0.000 title claims 7
- 230000000638 stimulation Effects 0.000 title abstract description 11
- 230000000694 effects Effects 0.000 claims abstract description 61
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 31
- 230000005764 inhibitory process Effects 0.000 claims abstract description 27
- 230000004580 weight loss Effects 0.000 claims abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 230000001939 inductive effect Effects 0.000 claims abstract description 3
- LTYOQGRJFJAKNA-IJCONWDESA-N malonyl-coenzyme a Chemical compound O[C@@H]1[C@@H](OP(O)(O)=O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-IJCONWDESA-N 0.000 claims description 62
- 239000003925 fat Substances 0.000 claims description 6
- 239000005557 antagonist Substances 0.000 claims description 5
- 229960004203 carnitine Drugs 0.000 claims description 5
- 235000013305 food Nutrition 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 235000014633 carbohydrates Nutrition 0.000 claims description 3
- 230000009897 systematic effect Effects 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- 230000006698 induction Effects 0.000 claims 1
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 51
- 229930195729 fatty acid Natural products 0.000 abstract description 51
- 239000000194 fatty acid Substances 0.000 abstract description 51
- 150000004665 fatty acids Chemical class 0.000 abstract description 51
- 230000003647 oxidation Effects 0.000 abstract description 45
- 238000007254 oxidation reaction Methods 0.000 abstract description 45
- 239000003814 drug Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 238000011161 development Methods 0.000 abstract description 3
- 230000004136 fatty acid synthesis Effects 0.000 abstract description 3
- LTYOQGRJFJAKNA-KKIMTKSISA-N Malonyl CoA Natural products S(C(=O)CC(=O)O)CCNC(=O)CCNC(=O)[C@@H](O)C(CO[P@](=O)(O[P@](=O)(OC[C@H]1[C@@H](OP(=O)(O)O)[C@@H](O)[C@@H](n2c3ncnc(N)c3nc2)O1)O)O)(C)C LTYOQGRJFJAKNA-KKIMTKSISA-N 0.000 abstract 2
- LTYOQGRJFJAKNA-DVVLENMVSA-N malonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-DVVLENMVSA-N 0.000 abstract 2
- 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 abstract 1
- 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- VCWLZDVWHQVAJU-UHFFFAOYSA-N 4-methylidene-2-octyl-5-oxotetrahydrofuran-3-carboxylic acid Chemical compound CCCCCCCCC1OC(=O)C(=C)C1C(O)=O VCWLZDVWHQVAJU-UHFFFAOYSA-N 0.000 description 86
- 210000004027 cell Anatomy 0.000 description 40
- 241000699670 Mus sp. Species 0.000 description 12
- 238000005070 sampling Methods 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 11
- 210000004185 liver Anatomy 0.000 description 9
- 230000004936 stimulating effect Effects 0.000 description 9
- 230000007423 decrease Effects 0.000 description 8
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 230000001413 cellular effect Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 6
- 210000001789 adipocyte Anatomy 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- GVEZIHKRYBHEFX-MNOVXSKESA-N 13C-Cerulenin Natural products CC=CCC=CCCC(=O)[C@H]1O[C@@H]1C(N)=O GVEZIHKRYBHEFX-MNOVXSKESA-N 0.000 description 5
- 102000015303 Fatty Acid Synthases Human genes 0.000 description 5
- 108010039731 Fatty Acid Synthases Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- GSLDEZOOOSBFGP-UHFFFAOYSA-N alpha-methylene gamma-butyrolactone Chemical class C=C1CCOC1=O GSLDEZOOOSBFGP-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- GVEZIHKRYBHEFX-UHFFFAOYSA-N caerulein A Natural products CC=CCC=CCCC(=O)C1OC1C(N)=O GVEZIHKRYBHEFX-UHFFFAOYSA-N 0.000 description 5
- GVEZIHKRYBHEFX-NQQPLRFYSA-N cerulenin Chemical compound C\C=C\C\C=C\CCC(=O)[C@H]1O[C@H]1C(N)=O GVEZIHKRYBHEFX-NQQPLRFYSA-N 0.000 description 5
- 229950005984 cerulenin Drugs 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000000577 adipose tissue Anatomy 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 230000002860 competitive effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- DZLOHEOHWICNIL-QGZVFWFLSA-N (2R)-2-[6-(4-chlorophenoxy)hexyl]-2-oxiranecarboxylic acid ethyl ester Chemical compound C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)OCC)CO1 DZLOHEOHWICNIL-QGZVFWFLSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 208000004930 Fatty Liver Diseases 0.000 description 2
- 206010019708 Hepatic steatosis Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
- 101000755720 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) Palmitoyltransferase akr1 Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 101100385142 Rattus norvegicus Cpt1a gene Proteins 0.000 description 2
- -1 acetyl coenzymes A Chemical compound 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 238000007707 calorimetry Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229950006213 etomoxir Drugs 0.000 description 2
- 230000004129 fatty acid metabolism Effects 0.000 description 2
- 208000010706 fatty liver disease Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000000803 paradoxical effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- PVSAPJKDKFIKHM-CQFAVKSRSA-N (3R)-3-hydroxy-3-(114C)methyl-4-(trimethylazaniumyl)butanoate Chemical compound [14CH3][C@](O)(C[N+](C)(C)C)CC([O-])=O PVSAPJKDKFIKHM-CQFAVKSRSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- MEFKEPWMEQBLKI-AIRLBKTGSA-O S-adenosyl-L-methionine Chemical class O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H]([NH3+])C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-O 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 125000001721 carboxyacetyl group Chemical group 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 101150043789 cpt2 gene Proteins 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 1
- UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000009246 food effect Effects 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- IPCSVZSSVZVIGE-VPMSBSONSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCC[14C](O)=O IPCSVZSSVZVIGE-VPMSBSONSA-N 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000005876 negative regulation of fatty acid oxidation Effects 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 238000013116 obese mouse model Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000008113 positive regulation of fatty acid oxidation Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
-
- 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
- G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Genetics & Genomics (AREA)
- Pediatric Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35448002P | 2002-02-08 | 2002-02-08 | |
| PCT/US2003/003839 WO2003066043A1 (en) | 2002-02-08 | 2003-02-10 | Stimulation of cpt-1 as a means to reduce weight |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200401052A1 EA200401052A1 (ru) | 2005-02-24 |
| EA007029B1 true EA007029B1 (ru) | 2006-06-30 |
Family
ID=27734382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200401052A EA007029B1 (ru) | 2002-02-08 | 2003-02-10 | Стимуляция срт-1 как средство уменьшения веса |
Country Status (12)
| Country | Link |
|---|---|
| US (4) | US20050143467A1 (https=) |
| EP (1) | EP1471906A4 (https=) |
| JP (2) | JP2005523270A (https=) |
| KR (1) | KR20040082417A (https=) |
| CN (1) | CN1313089C (https=) |
| AU (2) | AU2003215111A1 (https=) |
| BR (1) | BR0307421A (https=) |
| CA (1) | CA2474884A1 (https=) |
| EA (1) | EA007029B1 (https=) |
| IL (1) | IL163312A (https=) |
| MX (1) | MXPA04007556A (https=) |
| WO (1) | WO2003066043A1 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2474884A1 (en) * | 2002-02-08 | 2003-08-14 | John Hopkins University School Of Medicine | Stimulation of cpt-1 as a means to reduce weight |
| EA013371B1 (ru) * | 2002-07-09 | 2010-04-30 | Фасджен, Ллс. | Новые соединения, содержащие их фармацевтические композиции и способы их применения |
| WO2005089773A1 (en) * | 2004-03-18 | 2005-09-29 | Fasgen, Llc | Control of feeding behavior by changing neuronal energy balance |
| MXPA06013687A (es) * | 2004-05-26 | 2007-10-18 | Fasgen Llc | Compuestos novedosos, composiciones farmaceuticas que los contienen y metodos para utilizar los mismos. |
| BRPI0610877A2 (pt) * | 2005-06-06 | 2010-08-03 | Hoffmann La Roche | compostos, processo para a manufatura dos compostos, composições farmacêuticas que os compreendem, método para o tratamento terapêutico e/ou profilático de enfermidades que são moduladas por inibidores de l-cpt1 e utilização dos mesmos |
| WO2007014248A2 (en) * | 2005-07-26 | 2007-02-01 | Johns Hopkins University | Method of reducing food intake |
| ATE418603T1 (de) * | 2005-08-29 | 2009-01-15 | Hoffmann La Roche | Kristallstrukturen von carnitine palmitoyltransferase-2 (cpt-2) und deren verwendung |
| ES2405259B1 (es) * | 2011-11-25 | 2014-09-29 | Centro De Investigación Biomédica En Red Fisiopatología De La Obesidad Y Nutrición (Ciberobn) | Uso del enantiómero (+)-c75 para el tratamiento de la obesidad. |
| WO2013155528A2 (en) * | 2012-04-13 | 2013-10-17 | Fasgen, Inc. | Methods for reducing brain inflammation, increasing insulin sensitivity, and reducing ceramide levels |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US574639A (en) | 1897-01-05 | Gold-saving device | ||
| DE3026368A1 (de) * | 1980-07-11 | 1982-02-18 | Lentia GmbH Chem. u. pharm. Erzeugnisse - Industriebedarf, 8000 München | Naehrloesung fuer die vollstaendige parenterale ernaehrung und fuer gesteigerte energieproduktion |
| US5981575A (en) | 1996-11-15 | 1999-11-09 | Johns Hopkins University, The | Inhibition of fatty acid synthase as a means to reduce adipocyte mass |
| US5914326A (en) * | 1997-08-08 | 1999-06-22 | Ambi Inc. | Method for promoting weight and fat loss |
| US6413545B1 (en) * | 1998-09-01 | 2002-07-02 | Access Business Group International Llc | Diet composition and method of weight management |
| KR20090031957A (ko) * | 1999-11-12 | 2009-03-30 | 더 존스 홉킨스 유니버시티 | 세포내 말로닐 ＣｏＡ의 수준을 증가시킴에 의한 암의 치료방법 |
| WO2001060174A2 (en) * | 2000-02-16 | 2001-08-23 | The Johns Hopkins University School Of Medicine | Weight loss induced by reduction in neuropeptide y level |
| WO2002079501A1 (en) * | 2001-03-30 | 2002-10-10 | Trustees Of Boston University | Methods and reagents for identifying weight loss promoters and therapeutic uses therefor |
| CA2474884A1 (en) * | 2002-02-08 | 2003-08-14 | John Hopkins University School Of Medicine | Stimulation of cpt-1 as a means to reduce weight |
| US20040161803A1 (en) * | 2002-04-01 | 2004-08-19 | Corkey Barbara E. | Methods and reagents for identifying weight loss promoters and therpeutic uses therefor |
| US20060241177A1 (en) | 2002-07-01 | 2006-10-26 | Kuhadja Francis P | Novel compounds, pharmaceutical compositions containing same, and methods of use for same |
| EA013371B1 (ru) | 2002-07-09 | 2010-04-30 | Фасджен, Ллс. | Новые соединения, содержащие их фармацевтические композиции и способы их применения |
-
2003
- 2003-02-10 CA CA002474884A patent/CA2474884A1/en not_active Abandoned
- 2003-02-10 AU AU2003215111A patent/AU2003215111A1/en not_active Abandoned
- 2003-02-10 JP JP2003565467A patent/JP2005523270A/ja active Pending
- 2003-02-10 BR BR0307421-8A patent/BR0307421A/pt not_active IP Right Cessation
- 2003-02-10 WO PCT/US2003/003839 patent/WO2003066043A1/en not_active Ceased
- 2003-02-10 CN CNB038050145A patent/CN1313089C/zh not_active Expired - Fee Related
- 2003-02-10 EA EA200401052A patent/EA007029B1/ru unknown
- 2003-02-10 MX MXPA04007556A patent/MXPA04007556A/es active IP Right Grant
- 2003-02-10 KR KR10-2004-7012208A patent/KR20040082417A/ko not_active Ceased
- 2003-02-10 US US10/503,605 patent/US20050143467A1/en not_active Abandoned
- 2003-02-10 EP EP03710928A patent/EP1471906A4/en not_active Withdrawn
-
2004
- 2004-08-02 IL IL163312A patent/IL163312A/en not_active IP Right Cessation
- 2004-08-13 US US10/917,525 patent/US20050106217A1/en not_active Abandoned
-
2006
- 2006-10-02 US US11/537,968 patent/US7459481B2/en not_active Expired - Fee Related
-
2008
- 2008-11-06 US US12/266,425 patent/US20090124684A1/en not_active Abandoned
- 2008-11-20 AU AU2008249144A patent/AU2008249144A1/en not_active Abandoned
-
2009
- 2009-10-20 JP JP2009241309A patent/JP2010047594A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20050143467A1 (en) | 2005-06-30 |
| EP1471906A1 (en) | 2004-11-03 |
| CA2474884A1 (en) | 2003-08-14 |
| US20070087037A1 (en) | 2007-04-19 |
| US20050106217A1 (en) | 2005-05-19 |
| IL163312A (en) | 2011-12-29 |
| CN1638758A (zh) | 2005-07-13 |
| US7459481B2 (en) | 2008-12-02 |
| US20090124684A1 (en) | 2009-05-14 |
| JP2010047594A (ja) | 2010-03-04 |
| KR20040082417A (ko) | 2004-09-24 |
| WO2003066043A1 (en) | 2003-08-14 |
| AU2008249144A1 (en) | 2008-12-11 |
| EA200401052A1 (ru) | 2005-02-24 |
| EP1471906A4 (en) | 2006-02-01 |
| CN1313089C (zh) | 2007-05-02 |
| MXPA04007556A (es) | 2005-12-05 |
| JP2005523270A (ja) | 2005-08-04 |
| BR0307421A (pt) | 2004-12-28 |
| AU2003215111A1 (en) | 2003-09-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pålsson-McDermott et al. | Targeting immunometabolism as an anti-inflammatory strategy | |
| Ma et al. | BCAA–BCKA axis regulates WAT browning through acetylation of PRDM16 | |
| Liu et al. | An overview: the diversified role of mitochondria in cancer metabolism | |
| White et al. | Vascular contraction induced by activation of membrane calcium ion channels is enhanced in streptozotocin-diabetes. | |
| Xing et al. | Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK/PI3K/Akt/eNOS pathway | |
| Ahn et al. | MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin signaling | |
| Blankson et al. | Conjugated linoleic acid reduces body fat mass in overweight and obese humans | |
| Gleason et al. | Phorbol ester contracts rabbit thoracic aorta by increasing intracellular calcium and by activating calcium influx | |
| Gong et al. | Link between obesity and cancer: role of triglyceride/free fatty acid cycling | |
| Cong et al. | Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart | |
| JP2010047594A (ja) | 体重を減少させる方法としてのｃｐｔ−１の促進 | |
| Sajan et al. | Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C–ι | |
| Kollau et al. | Irreversible activation and stabilization of soluble guanylate cyclase by the protoporphyrin IX mimetic cinaciguat | |
| Oudaert et al. | Metabolic cross-talk within the bone marrow milieu: focus on multiple myeloma | |
| Hempenstall et al. | Dietary restriction increases skeletal muscle mitochondrial respiration but not mitochondrial content in C57BL/6 mice | |
| Horio et al. | Thermogenesis, low‐protein diets, and decreased development of AFB1‐induced preneoplastic foci in rat liver | |
| Nicholson et al. | Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia–reperfusion | |
| Tang et al. | Tumor necrosis factor-alpha upregulated PHLPP1 through activating nuclear factor-kappa B during myocardial ischemia/reperfusion | |
| Han et al. | β-Cell-protective effect of 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid as a glutamate dehydrogenase activator in db/db mice | |
| WO2000064431A9 (en) | Pharmaceutical compositions of tetrac and methods of use thereof | |
| Hironao et al. | The cacao procyanidin extract-caused anti-hyperglycemic effect was changed by the administration timings | |
| Xu et al. | Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer | |
| Soliman et al. | The synergistic effect of an ATP-competitive inhibitor of mtor and metformin on pancreatic tumor growth | |
| KR20120094308A (ko) | 2,4-비스(ｐ-하이드록시페닐)-2-부텐알을 유효성분으로 함유하는 염증 질환 또는 관절염 치료 및 예방용 약학조성물 | |
| Wise et al. | Possible role of dopamine-β-hydroxylase in the regulation of norepinephrine biosynthesis in rat brain |