AU2008214095B2 - Compositions and methods for the treatment of metabolic disorders - Google Patents

Info

Publication number

AU2008214095B2

AU2008214095B2 AU2008214095A AU2008214095A AU2008214095B2 AU 2008214095 B2 AU2008214095 B2 AU 2008214095B2 AU 2008214095 A AU2008214095 A AU 2008214095A AU 2008214095 A AU2008214095 A AU 2008214095A AU 2008214095 B2 AU2008214095 B2 AU 2008214095B2

Authority

AU

Australia

Prior art keywords

thiazol

propylpyridin

fatostatin

propylpyridine

phenyl

Prior art date

2007-02-02

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.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 208000030159 metabolic disease Diseases 0.000 title claims abstract description 44
• 239000000203 mixture Substances 0.000 title claims description 78
• 238000000034 method Methods 0.000 title claims description 55
• 238000011282 treatment Methods 0.000 title abstract description 40
• 150000001875 compounds Chemical class 0.000 claims abstract description 68
• 208000008589 Obesity Diseases 0.000 claims abstract description 26
• 235000020824 obesity Nutrition 0.000 claims abstract description 26
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 19
• 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 claims description 125
• 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 claims description 123
• 108010074436 Sterol Regulatory Element Binding Protein 1 Proteins 0.000 claims description 74
• 102100026839 Sterol regulatory element-binding protein 1 Human genes 0.000 claims description 73
• -1 p-toluenesulfonyl Chemical group 0.000 claims description 60
• 125000003118 aryl group Chemical group 0.000 claims description 29
• 108010074438 Sterol Regulatory Element Binding Protein 2 Proteins 0.000 claims description 23
• 102100026841 Sterol regulatory element-binding protein 2 Human genes 0.000 claims description 23
• 208000010706 fatty liver disease Diseases 0.000 claims description 23
• 208000004930 Fatty Liver Diseases 0.000 claims description 22
• 206010019708 Hepatic steatosis Diseases 0.000 claims description 22
• 150000003839 salts Chemical class 0.000 claims description 22
• 231100000240 steatosis hepatitis Toxicity 0.000 claims description 22
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 17
• 206010060862 Prostate cancer Diseases 0.000 claims description 16
• 235000005911 diet Nutrition 0.000 claims description 16
• 238000002560 therapeutic procedure Methods 0.000 claims description 16
• 230000037361 pathway Effects 0.000 claims description 15
• OWAXXHRQPWGNTG-UHFFFAOYSA-N n-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenyl]methanesulfonamide Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NS(C)(=O)=O)=CC=2)=C1 OWAXXHRQPWGNTG-UHFFFAOYSA-N 0.000 claims description 14
• GOKVUOGCZQKXQS-UHFFFAOYSA-N n-propan-2-yl-4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]aniline Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NC(C)C)=CC=2)=C1 GOKVUOGCZQKXQS-UHFFFAOYSA-N 0.000 claims description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
• QKFIOIFLEOWEFH-UHFFFAOYSA-N 4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]aniline Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(N)=CC=2)=C1 QKFIOIFLEOWEFH-UHFFFAOYSA-N 0.000 claims description 10
• VYYMYRPKZDHXOO-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C(=CC(F)=CC=2)F)=C1 VYYMYRPKZDHXOO-UHFFFAOYSA-N 0.000 claims description 9
• UIQZGUHSTKZKGY-UHFFFAOYSA-N 4-(2-methoxyphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C(=CC=CC=2)OC)=C1 UIQZGUHSTKZKGY-UHFFFAOYSA-N 0.000 claims description 9
• UBPWKUGAPZVWQE-UHFFFAOYSA-N 4-(3-methoxyphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=C(OC)C=CC=2)=C1 UBPWKUGAPZVWQE-UHFFFAOYSA-N 0.000 claims description 9
• OXTHFCVLLNTNRZ-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(3,4-dimethoxyphenyl)-1,3-thiazole Chemical compound C1=C(OC)C(OC)=CC=C1C1=NC(C=2C=CC(Cl)=CC=2)=CS1 OXTHFCVLLNTNRZ-UHFFFAOYSA-N 0.000 claims description 9
• LZVRJUVBTQEBPU-UHFFFAOYSA-N n-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenyl]acetamide Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NC(C)=O)=CC=2)=C1 LZVRJUVBTQEBPU-UHFFFAOYSA-N 0.000 claims description 9
• NJCQOVROHVLZKB-UHFFFAOYSA-N 2-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenol Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C(=CC=CC=2)O)=C1 NJCQOVROHVLZKB-UHFFFAOYSA-N 0.000 claims description 8
• QIYZIHGFQHSANG-UHFFFAOYSA-N 2-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenoxy]acetic acid Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(OCC(O)=O)=CC=2)=C1 QIYZIHGFQHSANG-UHFFFAOYSA-N 0.000 claims description 8
• HFSRZCFVFOUVKU-UHFFFAOYSA-N 3-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenol Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=C(O)C=CC=2)=C1 HFSRZCFVFOUVKU-UHFFFAOYSA-N 0.000 claims description 8
• VJLPOVIHSNLTQX-UHFFFAOYSA-N 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(Br)=CC=2)=C1 VJLPOVIHSNLTQX-UHFFFAOYSA-N 0.000 claims description 8
• FYTJKBDHCQUJQN-UHFFFAOYSA-N 4-(4-bromophenyl)-n-propan-2-yl-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxamide Chemical compound C1=NC(CCC)=CC(C=2SC(=C(N=2)C=2C=CC(Br)=CC=2)C(=O)NC(C)C)=C1 FYTJKBDHCQUJQN-UHFFFAOYSA-N 0.000 claims description 8
• UBVHKWIDYFYLLR-UHFFFAOYSA-N 4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenol Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(O)=CC=2)=C1 UBVHKWIDYFYLLR-UHFFFAOYSA-N 0.000 claims description 8
• UTQIDXTXWUQIBV-UHFFFAOYSA-N [4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenyl] benzoate Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(OC(=O)C=3C=CC=CC=3)=CC=2)=C1 UTQIDXTXWUQIBV-UHFFFAOYSA-N 0.000 claims description 8
• 238000011374 additional therapy Methods 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• JWEFKOCEVNIDGK-UHFFFAOYSA-N methyl 2-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenoxy]acetate Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(OCC(=O)OC)=CC=2)=C1 JWEFKOCEVNIDGK-UHFFFAOYSA-N 0.000 claims description 8
• NKZGVNISKULIAN-UHFFFAOYSA-N methyl 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxylate Chemical compound C1=NC(CCC)=CC(C=2SC(=C(N=2)C=2C=CC(Br)=CC=2)C(=O)OC)=C1 NKZGVNISKULIAN-UHFFFAOYSA-N 0.000 claims description 8
• BAQOAQCINMPNGC-UHFFFAOYSA-N n-benzyl-4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]aniline Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NCC=3C=CC=CC=3)=CC=2)=C1 BAQOAQCINMPNGC-UHFFFAOYSA-N 0.000 claims description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
• SXQHWZZWEJUUDI-UHFFFAOYSA-N 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=NC(CCC)=CC(C=2SC(=C(N=2)C=2C=CC(Br)=CC=2)C(O)=O)=C1 SXQHWZZWEJUUDI-UHFFFAOYSA-N 0.000 claims description 7
• 206010020772 Hypertension Diseases 0.000 claims description 7
• FMHQDMWHNYEVMV-UHFFFAOYSA-N n-(cyclopropylmethyl)-4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]aniline Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NCC3CC3)=CC=2)=C1 FMHQDMWHNYEVMV-UHFFFAOYSA-N 0.000 claims description 7
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 7
• 238000002651 drug therapy Methods 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• ATBCYIUPIXGWGZ-UHFFFAOYSA-N tert-butyl n-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenyl]carbamate Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NC(=O)OC(C)(C)C)=CC=2)=C1 ATBCYIUPIXGWGZ-UHFFFAOYSA-N 0.000 claims description 6
• FYCNBEGGRGPPBC-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 FYCNBEGGRGPPBC-UHFFFAOYSA-N 0.000 claims description 5
• QAIDAYZZJYOOJH-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(2-propyl-4-pyridinyl)thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(Cl)=CC=2)=C1 QAIDAYZZJYOOJH-UHFFFAOYSA-N 0.000 claims description 5
• IZEQQIVJQWJZCQ-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-phenyl-1,3-thiazole Chemical compound C1=CC(Cl)=CC=C1C1=CSC(C=2C=CC=CC=2)=N1 IZEQQIVJQWJZCQ-UHFFFAOYSA-N 0.000 claims description 5
• LGMZZYMIPZGPSU-UHFFFAOYSA-N 4-(4-ethylphenyl)-2-pyridin-4-yl-1,3-thiazole Chemical compound C1=CC(CC)=CC=C1C1=CSC(C=2C=CN=CC=2)=N1 LGMZZYMIPZGPSU-UHFFFAOYSA-N 0.000 claims description 5
• QKZNZFDVQQFDLV-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(F)=CC=2)=C1 QKZNZFDVQQFDLV-UHFFFAOYSA-N 0.000 claims description 5
• UVUVXLDIFQWHBY-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(OC)=CC=2)=C1 UVUVXLDIFQWHBY-UHFFFAOYSA-N 0.000 claims description 5
• 230000000378 dietary effect Effects 0.000 claims description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• ZCGDBTRLAJNWHJ-UHFFFAOYSA-N n-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenyl]thiophene-2-sulfonamide Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NS(=O)(=O)C=3SC=CC=3)=CC=2)=C1 ZCGDBTRLAJNWHJ-UHFFFAOYSA-N 0.000 claims description 5
• OHCBMYMUPIIOHV-UHFFFAOYSA-N 2-(2-propylpyridin-4-yl)-4-thiophen-2-yl-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2SC=CC=2)=C1 OHCBMYMUPIIOHV-UHFFFAOYSA-N 0.000 claims description 4
• ZNMIYSUPNOQXPL-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(2-ethylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CC)=CC(C=2SC=C(N=2)C=2C=CC(Cl)=CC=2)=C1 ZNMIYSUPNOQXPL-UHFFFAOYSA-N 0.000 claims description 4
• NNEPHBIYRFVPDJ-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-pyridin-4-yl-1,3-thiazole Chemical compound C1=CC(Cl)=CC=C1C1=CSC(C=2C=CN=CC=2)=N1 NNEPHBIYRFVPDJ-UHFFFAOYSA-N 0.000 claims description 4
• SKHJXKHKCQDSOX-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2-pyridin-4-yl-1,3-thiazole Chemical compound C1=CC(OC)=CC=C1C1=CSC(C=2C=CN=CC=2)=N1 SKHJXKHKCQDSOX-UHFFFAOYSA-N 0.000 claims description 4
• FCBWDNYFAULZCS-UHFFFAOYSA-N 4-(4-methylphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=NC(CCC)=CC(C=2SC(=C(N=2)C=2C=CC(C)=CC=2)C(O)=O)=C1 FCBWDNYFAULZCS-UHFFFAOYSA-N 0.000 claims description 4
• RGQZKXSQOVPMHZ-UHFFFAOYSA-N 4-(4-methylphenyl)-2-phenyl-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=CSC(C=2C=CC=CC=2)=N1 RGQZKXSQOVPMHZ-UHFFFAOYSA-N 0.000 claims description 4
• WHGCQPQZQBCMTM-UHFFFAOYSA-N 4-(4-methylphenyl)-2-pyridin-4-yl-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=CSC(C=2C=CN=CC=2)=N1 WHGCQPQZQBCMTM-UHFFFAOYSA-N 0.000 claims description 4
• YDCHGQNVVRRQLA-UHFFFAOYSA-N 4-phenyl-2-(2-propylpyridin-4-yl)-1,3-thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC=CC=2)=C1 YDCHGQNVVRRQLA-UHFFFAOYSA-N 0.000 claims description 4
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
• 201000005577 familial hyperlipidemia Diseases 0.000 claims description 4
• JKELRKVYOHHCPO-UHFFFAOYSA-N methyl 4-(4-methylphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxylate Chemical compound C1=NC(CCC)=CC(C=2SC(=C(N=2)C=2C=CC(C)=CC=2)C(=O)OC)=C1 JKELRKVYOHHCPO-UHFFFAOYSA-N 0.000 claims description 4
• RNMWGJXKUNRKSO-UHFFFAOYSA-N n-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenyl]quinoline-8-sulfonamide Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NS(=O)(=O)C=3C4=NC=CC=C4C=CC=3)=CC=2)=C1 RNMWGJXKUNRKSO-UHFFFAOYSA-N 0.000 claims description 4
• 238000000554 physical therapy Methods 0.000 claims description 4
• 238000001356 surgical procedure Methods 0.000 claims description 4
• 238000013542 behavioral therapy Methods 0.000 claims description 3
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 2
• 150000002148 esters Chemical class 0.000 claims description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
• PSIIDDOTVGEEHU-UHFFFAOYSA-N 4-methyl-n-[4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]phenyl]benzenesulfonamide Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NS(=O)(=O)C=3C=CC(C)=CC=3)=CC=2)=C1 PSIIDDOTVGEEHU-UHFFFAOYSA-N 0.000 claims 2
• KEAAJYWVSDRJIV-UHFFFAOYSA-N 4-phenyl-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=NC(CCC)=CC(C=2SC(=C(N=2)C=2C=CC=CC=2)C(O)=O)=C1 KEAAJYWVSDRJIV-UHFFFAOYSA-N 0.000 claims 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
• AKZYJUJVFCOXJZ-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2-pyridin-2-yl-1,3-thiazole Chemical compound C1=CC(OC)=CC=C1C1=CSC(C=2N=CC=CC=2)=N1 AKZYJUJVFCOXJZ-UHFFFAOYSA-N 0.000 claims 1
• MNSRRAREWYXSKP-UHFFFAOYSA-N 4-propan-2-yl-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxamide Chemical compound C(C)(C)C=1N=C(SC=1C(=O)N)C1=CC(=NC=C1)CCC MNSRRAREWYXSKP-UHFFFAOYSA-N 0.000 claims 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
• 150000001408 amides Chemical class 0.000 claims 1
• 229910052736 halogen Inorganic materials 0.000 claims 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
• ZROSUBKIGBSZCG-UHFFFAOYSA-N 4-(4-methylphenyl)-2-(2-propyl-4-pyridinyl)thiazole Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(C)=CC=2)=C1 ZROSUBKIGBSZCG-UHFFFAOYSA-N 0.000 abstract description 270
• 230000002265 prevention Effects 0.000 abstract description 11
• 241000699670 Mus sp. Species 0.000 description 158
• 210000004027 cell Anatomy 0.000 description 119
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 110
• 210000004185 liver Anatomy 0.000 description 99
• 108090000623 proteins and genes Proteins 0.000 description 92
• 230000000694 effects Effects 0.000 description 64
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 63
• 210000002966 serum Anatomy 0.000 description 50
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
• 235000012000 cholesterol Nutrition 0.000 description 46
• 102000004190 Enzymes Human genes 0.000 description 44
• 108090000790 Enzymes Proteins 0.000 description 44
• 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 43
• 108010039731 Fatty Acid Synthases Proteins 0.000 description 43
• 108010017037 SREBP cleavage-activating protein Proteins 0.000 description 40
• 102100027223 Sterol regulatory element-binding protein cleavage-activating protein Human genes 0.000 description 40
• 150000002632 lipids Chemical class 0.000 description 40
• 230000037396 body weight Effects 0.000 description 38
• 238000001994 activation Methods 0.000 description 37
• 230000015572 biosynthetic process Effects 0.000 description 36
• 235000014113 dietary fatty acids Nutrition 0.000 description 36
• 239000000284 extract Substances 0.000 description 36
• 239000000194 fatty acid Substances 0.000 description 36
• 229930195729 fatty acid Natural products 0.000 description 36
• 150000004665 fatty acids Chemical class 0.000 description 36
• 230000014509 gene expression Effects 0.000 description 36
• 230000003520 lipogenic effect Effects 0.000 description 36
• 235000018102 proteins Nutrition 0.000 description 35
• 102000004169 proteins and genes Human genes 0.000 description 35
• 239000000243 solution Substances 0.000 description 35
• 230000004913 activation Effects 0.000 description 34
• 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 32
• 239000012528 membrane Substances 0.000 description 32
• 239000003925 fat Substances 0.000 description 31
• 238000001262 western blot Methods 0.000 description 30
• 241001465754 Metazoa Species 0.000 description 29
• 241000699666 Mus <mouse, genus> Species 0.000 description 29
• 125000001072 heteroaryl group Chemical group 0.000 description 29
• 125000003368 amide group Chemical group 0.000 description 27
• 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 26
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 26
• 210000004369 blood Anatomy 0.000 description 26
• 239000008280 blood Substances 0.000 description 26
• 210000004379 membrane Anatomy 0.000 description 26
• 229930182558 Sterol Natural products 0.000 description 25
• 125000000304 alkynyl group Chemical group 0.000 description 25
• 239000008103 glucose Substances 0.000 description 25
• 239000002609 medium Substances 0.000 description 25
• 230000002829 reductive effect Effects 0.000 description 25
• 150000003432 sterols Chemical class 0.000 description 25
• 235000003702 sterols Nutrition 0.000 description 25
• 238000003786 synthesis reaction Methods 0.000 description 25
• 125000000217 alkyl group Chemical group 0.000 description 24
• 150000003626 triacylglycerols Chemical class 0.000 description 24
• 235000019439 ethyl acetate Nutrition 0.000 description 23
• 238000006467 substitution reaction Methods 0.000 description 22
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
• 108090000662 ATP citrate synthases Proteins 0.000 description 20
• 102000004146 ATP citrate synthases Human genes 0.000 description 20
• 210000002472 endoplasmic reticulum Anatomy 0.000 description 20
• 238000002474 experimental method Methods 0.000 description 20
• 235000012631 food intake Nutrition 0.000 description 20
• 230000003247 decreasing effect Effects 0.000 description 19
• 230000009467 reduction Effects 0.000 description 19
• 241000282414 Homo sapiens Species 0.000 description 18
• VRDIULHPQTYCLN-UHFFFAOYSA-N Prothionamide Chemical compound CCCC1=CC(C(N)=S)=CC=N1 VRDIULHPQTYCLN-UHFFFAOYSA-N 0.000 description 18
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 18
• 230000037406 food intake Effects 0.000 description 18
• 230000005764 inhibitory process Effects 0.000 description 18
• 239000002953 phosphate buffered saline Substances 0.000 description 18
• 108010001831 LDL receptors Proteins 0.000 description 17
• 102000000853 LDL receptors Human genes 0.000 description 17
• 102000040945 Transcription factor Human genes 0.000 description 17
• 108091023040 Transcription factor Proteins 0.000 description 17
• 230000011759 adipose tissue development Effects 0.000 description 17
• 239000002243 precursor Substances 0.000 description 17
• 230000002797 proteolythic effect Effects 0.000 description 17
• 230000001105 regulatory effect Effects 0.000 description 17
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 16
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 16
• 102000004877 Insulin Human genes 0.000 description 16
• 108090001061 Insulin Proteins 0.000 description 16
• ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-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)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 16
• 125000003342 alkenyl group Chemical group 0.000 description 16
• 230000007423 decrease Effects 0.000 description 16
• 239000003814 drug Substances 0.000 description 16
• 239000012091 fetal bovine serum Substances 0.000 description 16
• 230000012010 growth Effects 0.000 description 16
• 229940125396 insulin Drugs 0.000 description 16
• 239000007788 liquid Substances 0.000 description 16
• 230000003647 oxidation Effects 0.000 description 16
• 238000007254 oxidation reaction Methods 0.000 description 16
• 238000003757 reverse transcription PCR Methods 0.000 description 16
• 210000000577 adipose tissue Anatomy 0.000 description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
• 238000013518 transcription Methods 0.000 description 15
• 230000035897 transcription Effects 0.000 description 15
• 125000000753 cycloalkyl group Chemical group 0.000 description 14
• 230000002354 daily effect Effects 0.000 description 14
• 229940079593 drug Drugs 0.000 description 14
• 239000000463 material Substances 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019198 oils Nutrition 0.000 description 14
• 210000001519 tissue Anatomy 0.000 description 14
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 13
• 108060001084 Luciferase Proteins 0.000 description 13
• 239000005089 Luciferase Substances 0.000 description 13
• 230000007812 deficiency Effects 0.000 description 13
• 108020004999 messenger RNA Proteins 0.000 description 13
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 13
• 108010087894 Fatty acid desaturases Proteins 0.000 description 12
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 12
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 12
• 238000005481 NMR spectroscopy Methods 0.000 description 12
• 102000016553 Stearoyl-CoA Desaturase Human genes 0.000 description 12
• 150000001720 carbohydrates Chemical class 0.000 description 12
• 239000000470 constituent Substances 0.000 description 12
• 230000004136 fatty acid synthesis Effects 0.000 description 12
• 210000004940 nucleus Anatomy 0.000 description 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
• 239000004480 active ingredient Substances 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 11
• 230000037213 diet Effects 0.000 description 11
• 230000003828 downregulation Effects 0.000 description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
• 239000008194 pharmaceutical composition Substances 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• 102000007469 Actins Human genes 0.000 description 10
• 108010085238 Actins Proteins 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 102000057412 Diphosphomevalonate decarboxylases Human genes 0.000 description 10
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 10
• 101000958834 Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) Diphosphomevalonate decarboxylase mvd1 Proteins 0.000 description 10
• 101000958925 Panax ginseng Diphosphomevalonate decarboxylase 1 Proteins 0.000 description 10
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
• 235000014633 carbohydrates Nutrition 0.000 description 10
• 235000021588 free fatty acids Nutrition 0.000 description 10
• 238000011534 incubation Methods 0.000 description 10
• 230000004132 lipogenesis Effects 0.000 description 10
• 238000005259 measurement Methods 0.000 description 10
• 238000002360 preparation method Methods 0.000 description 10
• 150000003384 small molecules Chemical class 0.000 description 10
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 10
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 9
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 9
• 206010022489 Insulin Resistance Diseases 0.000 description 9
• 108700008625 Reporter Genes Proteins 0.000 description 9
• 101000895926 Streptomyces plicatus Endo-beta-N-acetylglucosaminidase H Proteins 0.000 description 9
• 238000004458 analytical method Methods 0.000 description 9
• 239000005516 coenzyme A Substances 0.000 description 9
• 229940093530 coenzyme a Drugs 0.000 description 9
• 125000004093 cyano group Chemical group *C#N 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• 235000013861 fat-free Nutrition 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 150000005830 nonesterified fatty acids Chemical class 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 101710194665 1-aminocyclopropane-1-carboxylate synthase Proteins 0.000 description 8
• WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 8
• 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 8
• 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 8
• 229930182555 Penicillin Natural products 0.000 description 8
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 8
• 229910004298 SiO 2 Inorganic materials 0.000 description 8
• 230000009471 action Effects 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 229960002685 biotin Drugs 0.000 description 8
• 239000011616 biotin Substances 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 201000010063 epididymitis Diseases 0.000 description 8
• 235000013305 food Nutrition 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 230000002440 hepatic effect Effects 0.000 description 8
• 230000006872 improvement Effects 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• 230000004060 metabolic process Effects 0.000 description 8
• 229910052757 nitrogen Inorganic materials 0.000 description 8
• 229940049954 penicillin Drugs 0.000 description 8
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
• 238000012545 processing Methods 0.000 description 8
• 239000011541 reaction mixture Substances 0.000 description 8
• 229960002385 streptomycin sulfate Drugs 0.000 description 8
• 102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 7
• 108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 7
• 108010018763 Biotin carboxylase Proteins 0.000 description 7
• 108020004414 DNA Proteins 0.000 description 7
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 7
• 238000007792 addition Methods 0.000 description 7
• 239000000443 aerosol Substances 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 230000010261 cell growth Effects 0.000 description 7
• 238000003776 cleavage reaction Methods 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 239000006185 dispersion Substances 0.000 description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
• 230000000144 pharmacologic effect Effects 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 230000007017 scission Effects 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 7
• 230000005945 translocation Effects 0.000 description 7
• KRVGXFREOJHJAX-UHFFFAOYSA-N 2-bromo-1-(4-methylphenyl)ethanone Chemical compound CC1=CC=C(C(=O)CBr)C=C1 KRVGXFREOJHJAX-UHFFFAOYSA-N 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• 101000581514 Homo sapiens Membrane-bound transcription factor site-2 protease Proteins 0.000 description 6
• 102100027382 Membrane-bound transcription factor site-2 protease Human genes 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 6
• 229920000037 Polyproline Polymers 0.000 description 6
• 108010029485 Protein Isoforms Proteins 0.000 description 6
• 102000001708 Protein Isoforms Human genes 0.000 description 6
• 108020004459 Small interfering RNA Proteins 0.000 description 6
• 235000001014 amino acid Nutrition 0.000 description 6
• 150000001413 amino acids Chemical class 0.000 description 6
• 230000033228 biological regulation Effects 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 239000000499 gel Substances 0.000 description 6
• 235000011187 glycerol Nutrition 0.000 description 6
• 208000007345 glycogen storage disease Diseases 0.000 description 6
• 125000000623 heterocyclic group Chemical group 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• 230000000670 limiting effect Effects 0.000 description 6
• 238000003468 luciferase reporter gene assay Methods 0.000 description 6
• 238000002493 microarray Methods 0.000 description 6
• 239000007758 minimum essential medium Substances 0.000 description 6
• 210000003205 muscle Anatomy 0.000 description 6
• 239000003755 preservative agent Substances 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 239000004055 small Interfering RNA Substances 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
• 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 5
• 101001076680 Homo sapiens Insulin-induced gene 1 protein Proteins 0.000 description 5
• 102100025887 Insulin-induced gene 1 protein Human genes 0.000 description 5
• 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 description 5
• 208000001145 Metabolic Syndrome Diseases 0.000 description 5
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 5
• 150000008052 alkyl sulfonates Chemical class 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 238000004113 cell culture Methods 0.000 description 5
• 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 5
• 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 5
• 235000002535 fat free diet Nutrition 0.000 description 5
• 210000002950 fibroblast Anatomy 0.000 description 5
• 239000012634 fragment Substances 0.000 description 5
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 5
• 201000001421 hyperglycemia Diseases 0.000 description 5
• 230000003993 interaction Effects 0.000 description 5
• 230000004807 localization Effects 0.000 description 5
• 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 description 5
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 5
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
• 239000003380 propellant Substances 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 239000000523 sample Substances 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 235000000346 sugar Nutrition 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• 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 4
• YZVFSQQHQPPKNX-UHFFFAOYSA-N 1,3-thiazole-5-carboxylic acid Chemical compound OC(=O)C1=CN=CS1 YZVFSQQHQPPKNX-UHFFFAOYSA-N 0.000 description 4
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
• INBGSXNNRGWLJU-ZHHJOTBYSA-N 25-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCCC(C)(C)O)C)[C@@]1(C)CC2 INBGSXNNRGWLJU-ZHHJOTBYSA-N 0.000 description 4
• INBGSXNNRGWLJU-UHFFFAOYSA-N 25epsilon-Hydroxycholesterin Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(CCCC(C)(C)O)C)C1(C)CC2 INBGSXNNRGWLJU-UHFFFAOYSA-N 0.000 description 4
• 101100478314 Caenorhabditis elegans sre-1 gene Proteins 0.000 description 4
• 238000000018 DNA microarray Methods 0.000 description 4
• 101710088194 Dehydrogenase Proteins 0.000 description 4
• 108010010234 HDL Lipoproteins Proteins 0.000 description 4
• 102000015779 HDL Lipoproteins Human genes 0.000 description 4
• 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 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
• 102000007330 LDL Lipoproteins Human genes 0.000 description 4
• 108010007622 LDL Lipoproteins Proteins 0.000 description 4
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
• 108091005804 Peptidases Proteins 0.000 description 4
• 239000004365 Protease Substances 0.000 description 4
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
• 238000011530 RNeasy Mini Kit Methods 0.000 description 4
• 239000012163 TRI reagent Substances 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• 125000002015 acyclic group Chemical group 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 239000011230 binding agent Substances 0.000 description 4
• 210000000170 cell membrane Anatomy 0.000 description 4
• 230000008859 change Effects 0.000 description 4
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• 210000004748 cultured cell Anatomy 0.000 description 4
• 230000001419 dependent effect Effects 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 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 4
• 230000002255 enzymatic effect Effects 0.000 description 4
• 230000003203 everyday effect Effects 0.000 description 4
• 230000004129 fatty acid metabolism Effects 0.000 description 4
• 125000001153 fluoro group Chemical group F* 0.000 description 4
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical group O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 4
• 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 4
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 230000006698 induction Effects 0.000 description 4
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
• 239000002502 liposome Substances 0.000 description 4
• 210000005228 liver tissue Anatomy 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• 244000005700 microbiome Species 0.000 description 4
• 235000021281 monounsaturated fatty acids Nutrition 0.000 description 4
• 239000013612 plasmid Substances 0.000 description 4
• SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 150000003457 sulfones Chemical class 0.000 description 4
• 150000003462 sulfoxides Chemical class 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• 230000000699 topical effect Effects 0.000 description 4
• 239000013598 vector Substances 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• 230000004580 weight loss Effects 0.000 description 4
• WAUMGXOXXFKMTR-UHFFFAOYSA-N 2-(2-ethylpyridin-4-yl)-4-(4-methylphenyl)-1,3-thiazole Chemical compound C1=NC(CC)=CC(C=2SC=C(N=2)C=2C=CC(C)=CC=2)=C1 WAUMGXOXXFKMTR-UHFFFAOYSA-N 0.000 description 3
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 3
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• 201000001320 Atherosclerosis Diseases 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 description 3
• 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 description 3
• 108700005857 Carnitine palmitoyl transferase 1A deficiency Proteins 0.000 description 3
• 208000005359 Carnitine palmitoyl transferase 1A deficiency Diseases 0.000 description 3
• 208000032928 Dyslipidaemia Diseases 0.000 description 3
• 206010053250 Glycogen storage disease type III Diseases 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
• 102100034343 Integrase Human genes 0.000 description 3
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• 102000004895 Lipoproteins Human genes 0.000 description 3
• 108090001030 Lipoproteins Proteins 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 108091034117 Oligonucleotide Proteins 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
• 102000035195 Peptidases Human genes 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical group C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 3
• 229940124639 Selective inhibitor Drugs 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 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 3
• 229930006000 Sucrose Natural products 0.000 description 3
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 108700036262 Trifunctional Protein Deficiency With Myopathy And Neuropathy Proteins 0.000 description 3
• 102000004142 Trypsin Human genes 0.000 description 3
• 108090000631 Trypsin Proteins 0.000 description 3
• 230000035508 accumulation Effects 0.000 description 3
• 238000009825 accumulation Methods 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 210000001789 adipocyte Anatomy 0.000 description 3
• 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 3
• 239000003098 androgen Substances 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 229940121375 antifungal agent Drugs 0.000 description 3
• 239000003429 antifungal agent Substances 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 238000010936 aqueous wash Methods 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 3
• 230000027455 binding Effects 0.000 description 3
• KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 3
• JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 3
• 125000001246 bromo group Chemical group Br* 0.000 description 3
• 230000005907 cancer growth Effects 0.000 description 3
• 201000004010 carnitine palmitoyltransferase I deficiency Diseases 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• 125000003636 chemical group Chemical group 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000000052 comparative effect Effects 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 229960003957 dexamethasone Drugs 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000002612 dispersion medium Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 230000004064 dysfunction Effects 0.000 description 3
• 230000002526 effect on cardiovascular system Effects 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 238000006911 enzymatic reaction Methods 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 235000013355 food flavoring agent Nutrition 0.000 description 3
• 235000003599 food sweetener Nutrition 0.000 description 3
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
• 229960004346 glimepiride Drugs 0.000 description 3
• 229960001381 glipizide Drugs 0.000 description 3
• 201000004502 glycogen storage disease II Diseases 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• 230000001976 improved effect Effects 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 125000002346 iodo group Chemical group I* 0.000 description 3
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical class CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 230000013190 lipid storage Effects 0.000 description 3
• 150000004668 long chain fatty acids Chemical class 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 229960003105 metformin Drugs 0.000 description 3
• 238000010172 mouse model Methods 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 150000003904 phospholipids Chemical class 0.000 description 3
• 230000026731 phosphorylation Effects 0.000 description 3
• 238000006366 phosphorylation reaction Methods 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 238000007639 printing Methods 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 239000012679 serum free medium Substances 0.000 description 3
• PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
• 238000003860 storage Methods 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 150000003871 sulfonates Chemical class 0.000 description 3
• 150000003460 sulfonic acids Chemical class 0.000 description 3
• 239000004094 surface-active agent Substances 0.000 description 3
• 239000003765 sweetening agent Substances 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 150000007979 thiazole derivatives Chemical class 0.000 description 3
• 239000012588 trypsin Substances 0.000 description 3
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 2
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 2
• PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
• 102100034542 Acyl-CoA (8-3)-desaturase Human genes 0.000 description 2
• 101710159293 Acyl-CoA desaturase 1 Proteins 0.000 description 2
• 229920000936 Agarose Polymers 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• 102100021334 Bcl-2-related protein A1 Human genes 0.000 description 2
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• 241000167854 Bourreria succulenta Species 0.000 description 2
• 208000014644 Brain disease Diseases 0.000 description 2
• 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• 201000000915 Chronic Progressive External Ophthalmoplegia Diseases 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 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 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
• 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
• 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
• 102000012737 Electron-Transferring Flavoproteins Human genes 0.000 description 2
• 108010079426 Electron-Transferring Flavoproteins Proteins 0.000 description 2
• 208000032274 Encephalopathy Diseases 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 208000006562 Glycogen Storage Disease Type VII Diseases 0.000 description 2
• 208000011123 Glycogen storage disease due to glycogen branching enzyme deficiency Diseases 0.000 description 2
• 208000032000 Glycogen storage disease due to muscle glycogen phosphorylase deficiency Diseases 0.000 description 2
• 206010018464 Glycogen storage disease type I Diseases 0.000 description 2
• 206010053185 Glycogen storage disease type II Diseases 0.000 description 2
• 206010018462 Glycogen storage disease type V Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
• 206010019842 Hepatomegaly Diseases 0.000 description 2
• 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 2
• 101000677540 Homo sapiens Acetyl-CoA carboxylase 2 Proteins 0.000 description 2
• 101000894929 Homo sapiens Bcl-2-related protein A1 Proteins 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 101150088952 IGF1 gene Proteins 0.000 description 2
• 208000001019 Inborn Errors Metabolism Diseases 0.000 description 2
• 206010048804 Kearns-Sayre syndrome Diseases 0.000 description 2
• 201000000639 Leber hereditary optic neuropathy Diseases 0.000 description 2
• 108010092277 Leptin Proteins 0.000 description 2
• 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 2
• 102000003960 Ligases Human genes 0.000 description 2
• 108090000364 Ligases Proteins 0.000 description 2
• 102000004882 Lipase Human genes 0.000 description 2
• 108090001060 Lipase Proteins 0.000 description 2
• 102000004317 Lyases Human genes 0.000 description 2
• 108090000856 Lyases Proteins 0.000 description 2
• 201000009035 MERRF syndrome Diseases 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 108700000232 Medium chain acyl CoA dehydrogenase deficiency Proteins 0.000 description 2
• 206010072654 Medium-chain acyl-coenzyme A dehydrogenase deficiency Diseases 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 102100022259 Mevalonate kinase Human genes 0.000 description 2
• 108700040132 Mevalonate kinases Proteins 0.000 description 2
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 2
• 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 description 2
• 241000699660 Mus musculus Species 0.000 description 2
• 206010069825 Myoclonic epilepsy and ragged-red fibres Diseases 0.000 description 2
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
• 102000004316 Oxidoreductases Human genes 0.000 description 2
• 108090000854 Oxidoreductases Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 206010036802 Progressive external ophthalmoplegia Diseases 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
• 239000013614 RNA sample Substances 0.000 description 2
• 238000011529 RT qPCR Methods 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• 206010072656 Very long-chain acyl-coenzyme A dehydrogenase deficiency Diseases 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 239000011543 agarose gel Substances 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 230000000390 anti-adipogenic effect Effects 0.000 description 2
• 230000000844 anti-bacterial effect Effects 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 239000012736 aqueous medium Substances 0.000 description 2
• 229940062310 avandia Drugs 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 235000020958 biotin Nutrition 0.000 description 2
• 238000009534 blood test Methods 0.000 description 2
• 229910021538 borax Inorganic materials 0.000 description 2
• UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 229960004203 carnitine Drugs 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 235000019693 cherries Nutrition 0.000 description 2
• 229960004926 chlorobutanol Drugs 0.000 description 2
• 229960001231 choline Drugs 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 229940099112 cornstarch Drugs 0.000 description 2
• 230000000875 corresponding effect Effects 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 239000000287 crude extract Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 230000001186 cumulative effect Effects 0.000 description 2
• 210000000805 cytoplasm Anatomy 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• TYNBFJJKZPTRKS-UHFFFAOYSA-N dansyl amide Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(N)(=O)=O TYNBFJJKZPTRKS-UHFFFAOYSA-N 0.000 description 2
• 238000012217 deletion Methods 0.000 description 2
• 230000037430 deletion Effects 0.000 description 2
• 238000004925 denaturation Methods 0.000 description 2
• 230000036425 denaturation Effects 0.000 description 2
• 239000000551 dentifrice Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 208000016097 disease of metabolism Diseases 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
• 239000013604 expression vector Substances 0.000 description 2
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 230000030279 gene silencing Effects 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
• 201000004541 glycogen storage disease I Diseases 0.000 description 2
• 201000004534 glycogen storage disease V Diseases 0.000 description 2
• 210000002288 golgi apparatus Anatomy 0.000 description 2
• 230000009716 hepatic expression Effects 0.000 description 2
• 230000013632 homeostatic process Effects 0.000 description 2
• 235000011167 hydrochloric acid Nutrition 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 229910052739 hydrogen Inorganic materials 0.000 description 2
• 230000003345 hyperglycaemic effect Effects 0.000 description 2
• 238000010166 immunofluorescence Methods 0.000 description 2
• 238000012744 immunostaining Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 208000016245 inborn errors of metabolism Diseases 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 230000036512 infertility Effects 0.000 description 2
• 208000015978 inherited metabolic disease Diseases 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 210000001596 intra-abdominal fat Anatomy 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 239000007951 isotonicity adjuster Substances 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 108010052968 leupeptin Proteins 0.000 description 2
• 230000004130 lipolysis Effects 0.000 description 2
• 238000011068 loading method Methods 0.000 description 2
• 208000026695 long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Diseases 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 229960002510 mandelic acid Drugs 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 238000013507 mapping Methods 0.000 description 2
• 208000005548 medium chain acyl-CoA dehydrogenase deficiency Diseases 0.000 description 2
• OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 2
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
• 238000010208 microarray analysis Methods 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 208000012268 mitochondrial disease Diseases 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 230000003990 molecular pathway Effects 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 239000002324 mouth wash Substances 0.000 description 2
• 229940051866 mouthwash Drugs 0.000 description 2
• TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• NOWKPAMUTSDVKG-UHFFFAOYSA-N n-cyclohexyl-4-[2-(2-propylpyridin-4-yl)-1,3-thiazol-4-yl]aniline Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(NC3CCCCC3)=CC=2)=C1 NOWKPAMUTSDVKG-UHFFFAOYSA-N 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 2
• 235000021590 normal diet Nutrition 0.000 description 2
• 238000010606 normalization Methods 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 230000030648 nucleus localization Effects 0.000 description 2
• 238000013116 obese mouse model Methods 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 229920001542 oligosaccharide Polymers 0.000 description 2
• 150000002482 oligosaccharides Chemical class 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 239000006072 paste Substances 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• 108010091212 pepstatin Proteins 0.000 description 2
• 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 2
• 229960003742 phenol Drugs 0.000 description 2
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
• 235000011007 phosphoric acid Nutrition 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 108010026466 polyproline Proteins 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
• 230000017854 proteolysis Effects 0.000 description 2
• 229960000918 protionamide Drugs 0.000 description 2
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 239000002510 pyrogen Substances 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 238000011002 quantification Methods 0.000 description 2
• 238000009790 rate-determining step (RDS) Methods 0.000 description 2
• 238000003753 real-time PCR Methods 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
• 229940054269 sodium pyruvate Drugs 0.000 description 2
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• 235000010339 sodium tetraborate Nutrition 0.000 description 2
• JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 2
• 235000010199 sorbic acid Nutrition 0.000 description 2
• 239000004334 sorbic acid Substances 0.000 description 2
• 229940075582 sorbic acid Drugs 0.000 description 2
• 238000001179 sorption measurement Methods 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 238000010186 staining Methods 0.000 description 2
• SIARJEKBADXQJG-LFZQUHGESA-N stearoyl-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)CCCCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SIARJEKBADXQJG-LFZQUHGESA-N 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
• 229940033663 thimerosal Drugs 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000002103 transcriptional effect Effects 0.000 description 2
• 238000011830 transgenic mouse model Methods 0.000 description 2
• 230000032258 transport Effects 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 2
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 2
• 229960001641 troglitazone Drugs 0.000 description 2
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
• 201000010866 very long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 description 2
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 2
• 229960001254 vildagliptin Drugs 0.000 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• GQPYTJVDPQTBQC-KLQYNRQASA-N (3r)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F GQPYTJVDPQTBQC-KLQYNRQASA-N 0.000 description 1
• YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
• KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 102000003925 1,4-alpha-Glucan Branching Enzyme Human genes 0.000 description 1
• 108090000344 1,4-alpha-Glucan Branching Enzyme Proteins 0.000 description 1
• AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• KVUXYQHEESDGIJ-UHFFFAOYSA-N 10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthrene-3,16-diol Chemical compound C1CC2CC(O)CCC2(C)C2C1C1CC(O)CC1(C)CC2 KVUXYQHEESDGIJ-UHFFFAOYSA-N 0.000 description 1
• OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• 108700032300 2,4-Dienoyl-CoA Reductase Deficiency Proteins 0.000 description 1
• XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
• 108700028607 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency Proteins 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• 208000024801 3-hydroxy-3-methylglutaric aciduria Diseases 0.000 description 1
• 208000009270 3-hydroxyacyl-CoA dehydrogenase deficiency Diseases 0.000 description 1
• YLPWNTDEIXFTQQ-UHFFFAOYSA-N 4-(3-methoxyphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole;methyl 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole-5-carboxylate Chemical compound C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=C(OC)C=CC=2)=C1.C1=NC(CCC)=CC(C=2SC(=C(N=2)C=2C=CC(Br)=CC=2)C(=O)OC)=C1 YLPWNTDEIXFTQQ-UHFFFAOYSA-N 0.000 description 1
• SQTRQBDBNAQWHG-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-pyridin-2-yl-1,3-thiazole Chemical compound C1=CC(Cl)=CC=C1C1=CSC(C=2N=CC=CC=2)=N1 SQTRQBDBNAQWHG-UHFFFAOYSA-N 0.000 description 1
• RJCFNQZVFUMORB-UHFFFAOYSA-N 4-(4-methylphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole;hydrobromide Chemical class Br.C1=NC(CCC)=CC(C=2SC=C(N=2)C=2C=CC(C)=CC=2)=C1 RJCFNQZVFUMORB-UHFFFAOYSA-N 0.000 description 1
• UEFFIKGPZCFIHD-UHFFFAOYSA-N 4-(4-methylphenyl)-2-pyridin-2-yl-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=CSC(C=2N=CC=CC=2)=N1 UEFFIKGPZCFIHD-UHFFFAOYSA-N 0.000 description 1
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
• GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
• RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
• HCEQQASHRRPQFE-UHFFFAOYSA-N 5-chloro-n-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide;3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N.COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 HCEQQASHRRPQFE-UHFFFAOYSA-N 0.000 description 1
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• JDDWRLPTKIOUOF-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-[[4-[2-[bis(4-methylphenyl)methylamino]-2-oxoethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]carbamate Chemical compound COC1=CC(OC)=CC=C1C(C=1C=CC(OCC(=O)NC(C=2C=CC(C)=CC=2)C=2C=CC(C)=CC=2)=CC=1)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 JDDWRLPTKIOUOF-UHFFFAOYSA-N 0.000 description 1
• 102000008146 Acetate-CoA ligase Human genes 0.000 description 1
• 108010049926 Acetate-CoA ligase Proteins 0.000 description 1
• 101710102367 Acyl-CoA (8-3)-desaturase Proteins 0.000 description 1
• 102100035785 Acyl-CoA-binding protein Human genes 0.000 description 1
• 244000153158 Ammi visnaga Species 0.000 description 1
• 235000010585 Ammi visnaga Nutrition 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 206010003591 Ataxia Diseases 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 229940123208 Biguanide Drugs 0.000 description 1
• 101710133654 C-5 sterol desaturase Proteins 0.000 description 1
• 101100268668 Caenorhabditis elegans acc-2 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
• 102000004031 Carboxy-Lyases Human genes 0.000 description 1
• 108090000489 Carboxy-Lyases Proteins 0.000 description 1
• 108700005858 Carnitine palmitoyl transferase 2 deficiency Proteins 0.000 description 1
• 201000002929 Carnitine palmitoyltransferase II deficiency Diseases 0.000 description 1
• 108700017419 Carnitine-Acylcarnitine Translocase Deficiency Proteins 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 108050000084 Caveolin Proteins 0.000 description 1
• 102000009193 Caveolin Human genes 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 108010036824 Citrate (pro-3S)-lyase Proteins 0.000 description 1
• VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 description 1
• 229920000742 Cotton Polymers 0.000 description 1
• 101150073133 Cpt1a gene Proteins 0.000 description 1
• 102100023583 Cyclic AMP-dependent transcription factor ATF-6 alpha Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical group OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 1
• 206010011878 Deafness Diseases 0.000 description 1
• 101710111046 Delta(7)-sterol 5(6)-desaturase Proteins 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 108010039287 Diazepam Binding Inhibitor Proteins 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 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
• DWAWDSVKAUWFHC-UHFFFAOYSA-N Emopamil Chemical compound C=1C=CC=CC=1C(C(C)C)(C#N)CCCN(C)CCC1=CC=CC=C1 DWAWDSVKAUWFHC-UHFFFAOYSA-N 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 108700024394 Exon Proteins 0.000 description 1
• 206010015995 Eyelid ptosis Diseases 0.000 description 1
• 101150064015 FAS gene Proteins 0.000 description 1
• 208000024720 Fabry Disease Diseases 0.000 description 1
• 208000001948 Farber Lipogranulomatosis Diseases 0.000 description 1
• 102100035111 Farnesyl pyrophosphate synthase Human genes 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 229930091371 Fructose Natural products 0.000 description 1
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
• 239000005715 Fructose Substances 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 102000002464 Galactosidases Human genes 0.000 description 1
• 108010093031 Galactosidases Proteins 0.000 description 1
• 208000009796 Gangliosidoses Diseases 0.000 description 1
• 208000015872 Gaucher disease Diseases 0.000 description 1
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
• 229930182566 Gentamicin Natural products 0.000 description 1
• 108010026318 Geranyltranstransferase Proteins 0.000 description 1
• 102000042092 Glucose transporter family Human genes 0.000 description 1
• 108091052347 Glucose transporter family Proteins 0.000 description 1
• 102000004366 Glucosidases Human genes 0.000 description 1
• 108010056771 Glucosidases Proteins 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical group OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 101710091951 Glycerol-3-phosphate acyltransferase Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 206010053249 Glycogen Storage Disease Type IV Diseases 0.000 description 1
• 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
• 208000032003 Glycogen storage disease due to glucose-6-phosphatase deficiency Diseases 0.000 description 1
• 208000032008 Glycogen storage disease due to glycogen debranching enzyme deficiency Diseases 0.000 description 1
• 208000032002 Glycogen storage disease due to liver glycogen phosphorylase deficiency Diseases 0.000 description 1
• 208000031926 Glycogen storage disease due to muscle phosphofructokinase deficiency Diseases 0.000 description 1
• 208000014324 Glycogen storage disease due to phosphorylase kinase deficiency Diseases 0.000 description 1
• 229930186217 Glycolipid Natural products 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000905751 Homo sapiens Cyclic AMP-dependent transcription factor ATF-6 alpha Proteins 0.000 description 1
• 101000629605 Homo sapiens Sterol regulatory element-binding protein 2 Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 1
• 102100028889 Hydroxymethylglutaryl-CoA synthase, mitochondrial Human genes 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 108090000769 Isomerases Proteins 0.000 description 1
• 102000004195 Isomerases Human genes 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• 238000008214 LDL Cholesterol Methods 0.000 description 1
• 239000004166 Lanolin Substances 0.000 description 1
• 102100032011 Lanosterol synthase Human genes 0.000 description 1
• 108010059597 Lanosterol synthase Proteins 0.000 description 1
• 101710137448 Lathosterol oxidase Proteins 0.000 description 1
• 102100037199 Lathosterol oxidase Human genes 0.000 description 1
• 208000006136 Leigh Disease Diseases 0.000 description 1
• 208000017507 Leigh syndrome Diseases 0.000 description 1
• 102000016267 Leptin Human genes 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 239000004367 Lipase Substances 0.000 description 1
• 208000017170 Lipid metabolism disease Diseases 0.000 description 1
• 208000010557 Lipid storage disease Diseases 0.000 description 1
• 108010013563 Lipoprotein Lipase Proteins 0.000 description 1
• 102100022119 Lipoprotein lipase Human genes 0.000 description 1
• 102000018653 Long-Chain Acyl-CoA Dehydrogenase Human genes 0.000 description 1
• 108010027062 Long-Chain Acyl-CoA Dehydrogenase Proteins 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 108700004450 Malonic aciduria Proteins 0.000 description 1
• 208000003160 Malonic aciduria Diseases 0.000 description 1
• GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 108010062495 Mediator Complex Subunit 1 Proteins 0.000 description 1
• 244000246386 Mentha pulegium Species 0.000 description 1
• 235000016257 Mentha pulegium Nutrition 0.000 description 1
• 235000004357 Mentha x piperita Nutrition 0.000 description 1
• 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 1
• TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
• 102000006833 Multifunctional Enzymes Human genes 0.000 description 1
• 108010047290 Multifunctional Enzymes Proteins 0.000 description 1
• 241000238367 Mya arenaria Species 0.000 description 1
• 102100032394 N-acetyltransferase 8 Human genes 0.000 description 1
• 101710092255 N-acetyltransferase 8 Proteins 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 208000014060 Niemann-Pick disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 206010033307 Overweight Diseases 0.000 description 1
• 102000000536 PPAR gamma Human genes 0.000 description 1
• 108010016731 PPAR gamma Proteins 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 102000014750 Phosphorylase Kinase Human genes 0.000 description 1
• 108010064071 Phosphorylase Kinase Proteins 0.000 description 1
• 102000009097 Phosphorylases Human genes 0.000 description 1
• 108010073135 Phosphorylases Proteins 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000028269 Progressive encephalopathy with leukodystrophy due to DECR deficiency Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 101000906384 Rattus norvegicus Glutathione S-transferase Mu 7 Proteins 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 102000006382 Ribonucleases Human genes 0.000 description 1
• 108010083644 Ribonucleases Proteins 0.000 description 1
• 239000012722 SDS sample buffer Substances 0.000 description 1
• AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
• 101000757182 Saccharomyces cerevisiae Glucoamylase S2 Proteins 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 101001083555 Sus scrofa Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Proteins 0.000 description 1
• 208000001163 Tangier disease Diseases 0.000 description 1
• BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 229940122618 Trypsin inhibitor Drugs 0.000 description 1
• 101710162629 Trypsin inhibitor Proteins 0.000 description 1
• 208000026589 Wolman disease Diseases 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
• 239000003082 abrasive agent Substances 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 229960002632 acarbose Drugs 0.000 description 1
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
• 102000005421 acetyltransferase Human genes 0.000 description 1
• 108020002494 acetyltransferase Proteins 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 229940062328 actos Drugs 0.000 description 1
• 208000005652 acute fatty liver of pregnancy Diseases 0.000 description 1
• 210000000593 adipose tissue white Anatomy 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 125000001118 alkylidene group Chemical group 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 229940000806 amaryl Drugs 0.000 description 1
• 230000001668 ameliorated effect Effects 0.000 description 1
• 229960002684 aminocaproic acid Drugs 0.000 description 1
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
• 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
• 230000000845 anti-microbial effect Effects 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 125000001769 aryl amino group Chemical group 0.000 description 1
• 125000004421 aryl sulphonamide group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 229940054739 avandamet Drugs 0.000 description 1
• 229940111640 avandaryl Drugs 0.000 description 1
• 238000003287 bathing Methods 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 238000012742 biochemical analysis Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 229960000074 biopharmaceutical Drugs 0.000 description 1
• 230000001851 biosynthetic effect Effects 0.000 description 1
• 229940046011 buccal tablet Drugs 0.000 description 1
• 239000006189 buccal tablet Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 230000023852 carbohydrate metabolic process Effects 0.000 description 1
• 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 230000021523 carboxylation Effects 0.000 description 1
• 238000006473 carboxylation reaction Methods 0.000 description 1
• 208000005071 carnitine-acylcarnitine translocase deficiency Diseases 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 230000004640 cellular pathway Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000007958 cherry flavor Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 208000024042 cholesterol ester storage disease Diseases 0.000 description 1
• 150000001840 cholesterol esters Chemical class 0.000 description 1
• 150000001841 cholesterols Chemical class 0.000 description 1
• 208000013760 cholesteryl ester storage disease Diseases 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000008294 cold cream Substances 0.000 description 1
• 239000000084 colloidal system Substances 0.000 description 1
• 238000004737 colorimetric analysis Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 239000012050 conventional carrier Substances 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 235000021316 daily nutritional intake Nutrition 0.000 description 1
• 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
• 231100000895 deafness Toxicity 0.000 description 1
• 230000007123 defense Effects 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 230000030609 dephosphorylation Effects 0.000 description 1
• 238000006209 dephosphorylation reaction Methods 0.000 description 1
• 230000008021 deposition Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 235000013367 dietary fats Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• VLYUGYAKYZETRF-UHFFFAOYSA-N dihydrolipoamide Chemical compound NC(=O)CCCCC(S)CCS VLYUGYAKYZETRF-UHFFFAOYSA-N 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical group CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 230000002222 downregulating effect Effects 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 229940012584 duetact Drugs 0.000 description 1
• 229950009967 emopamil Drugs 0.000 description 1
• 238000004945 emulsification Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• 230000030583 endoplasmic reticulum localization Effects 0.000 description 1
• 230000037149 energy metabolism Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 210000001842 enterocyte Anatomy 0.000 description 1
• 108010017796 epoxidase Proteins 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
• 238000013265 extended release Methods 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000002185 fatty acyl-CoAs Chemical group 0.000 description 1
• 231100000502 fertility decrease Toxicity 0.000 description 1
• 208000018634 fetal akinesia deformation sequence Diseases 0.000 description 1
• 208000012165 fetal akinesia deformation sequence syndrome Diseases 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001917 fluorescence detection Methods 0.000 description 1
• 238000002421 fluorescence-activated droplet sorting Methods 0.000 description 1
• 239000004088 foaming agent Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 239000003349 gelling agent Substances 0.000 description 1
• 102000034356 gene-regulatory proteins Human genes 0.000 description 1
• 108091006104 gene-regulatory proteins Proteins 0.000 description 1
• 230000009395 genetic defect Effects 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 229960004580 glibenclamide Drugs 0.000 description 1
• 239000000174 gluconic acid Chemical group 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229940095884 glucophage Drugs 0.000 description 1
• 229940112611 glucovance Drugs 0.000 description 1
• 239000004220 glutamic acid Chemical group 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
• 229940001962 glyburide / metformin Drugs 0.000 description 1
• 150000002327 glycerophospholipids Chemical class 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 201000004543 glycogen storage disease III Diseases 0.000 description 1
• 201000004510 glycogen storage disease VI Diseases 0.000 description 1
• 201000009339 glycogen storage disease VII Diseases 0.000 description 1
• 208000019061 glycogen storage disease due to GLUT2 deficiency Diseases 0.000 description 1
• 150000002339 glycosphingolipids Chemical class 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 229940084937 glyset Drugs 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 238000000227 grinding Methods 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 208000016354 hearing loss disease Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 108010064060 high density lipoprotein receptors Proteins 0.000 description 1
• 235000009200 high fat diet Nutrition 0.000 description 1
• 102000054823 high-density lipoprotein particle receptor activity proteins Human genes 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 235000001050 hortel pimenta Nutrition 0.000 description 1
• 102000049151 human SREBF2 Human genes 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 230000000910 hyperinsulinemic effect Effects 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 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
• 239000007972 injectable composition Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 229940090473 januvia Drugs 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 208000006443 lactic acidosis Diseases 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
• 229940039781 leptin Drugs 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
• 235000019421 lipase Nutrition 0.000 description 1
• 230000006372 lipid accumulation Effects 0.000 description 1
• 230000004322 lipid homeostasis Effects 0.000 description 1
• 230000008604 lipoprotein metabolism Effects 0.000 description 1
• 238000007443 liposuction Methods 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 235000004213 low-fat Nutrition 0.000 description 1
• 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 208000014416 lysosomal lipid storage disease Diseases 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 229940045623 meridia Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000037353 metabolic pathway Effects 0.000 description 1
• 230000037323 metabolic rate Effects 0.000 description 1
• 229940054183 metaglip Drugs 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 229960004329 metformin hydrochloride Drugs 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
• AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
• BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
• 239000000693 micelle Substances 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 230000003228 microsomal effect Effects 0.000 description 1
• 229960001110 miglitol Drugs 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 208000014305 mitochondrial trifunctional protein deficiency Diseases 0.000 description 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 239000003068 molecular probe Substances 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 229940105132 myristate Drugs 0.000 description 1
• JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 210000000633 nuclear envelope Anatomy 0.000 description 1
• 230000005937 nuclear translocation Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• XDUHQPOXLUAVEE-BPMMELMSSA-N oleoyl-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)CCCCCCC\C=C/CCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 XDUHQPOXLUAVEE-BPMMELMSSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 229940100688 oral solution Drugs 0.000 description 1
• 239000000668 oral spray Substances 0.000 description 1
• 229940041678 oral spray Drugs 0.000 description 1
• 239000007968 orange flavor Substances 0.000 description 1
• 210000003463 organelle Anatomy 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
• 229960001243 orlistat Drugs 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• QBYOCCWNZAOZTL-MDMKAECGSA-N palmitoleoyl-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)CCCCCCC\C=C/CCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QBYOCCWNZAOZTL-MDMKAECGSA-N 0.000 description 1
• MNBKLUUYKPBKDU-BBECNAHFSA-N palmitoyl-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)CCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MNBKLUUYKPBKDU-BBECNAHFSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 210000001986 peyer's patch Anatomy 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229960003562 phentermine Drugs 0.000 description 1
• CKOOABJZYWLHMN-UHFFFAOYSA-N phenyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1=CC=CC=C1.C=1C=CC=CC=1C(=O)OC1=CC=CC=C1 CKOOABJZYWLHMN-UHFFFAOYSA-N 0.000 description 1
• 150000003016 phosphoric acids Chemical class 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 235000007686 potassium Nutrition 0.000 description 1
• 235000015497 potassium bicarbonate Nutrition 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940116317 potato starch Drugs 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229940096058 prandin Drugs 0.000 description 1
• 229940095885 precose Drugs 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 201000003004 ptosis Diseases 0.000 description 1
• 150000004040 pyrrolidinones Chemical class 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 229960003271 rosiglitazone maleate Drugs 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 235000003441 saturated fatty acids Nutrition 0.000 description 1
• 150000004671 saturated fatty acids Chemical class 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000028201 sequestering of triglyceride Effects 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 208000001392 short chain acyl-CoA dehydrogenase deficiency Diseases 0.000 description 1
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
• 229960004425 sibutramine Drugs 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 229960004115 sitagliptin phosphate Drugs 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• RIYNLCMADQUBEM-FYZOBXCZSA-M sodium;(3r)-3,5-dihydroxy-3-methylpentanoate Chemical compound [Na+].OCC[C@](O)(C)CC([O-])=O RIYNLCMADQUBEM-FYZOBXCZSA-M 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 229940032094 squalane Drugs 0.000 description 1
• 229940031439 squalene Drugs 0.000 description 1
• TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
• 235000000891 standard diet Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 229940110862 starlix Drugs 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 238000005556 structure-activity relationship Methods 0.000 description 1
• 230000004960 subcellular localization Effects 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 150000003505 terpenes Chemical class 0.000 description 1
• 235000007586 terpenes Nutrition 0.000 description 1
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
• RTZRUVMEWWPNRR-UHFFFAOYSA-N tert-butyl n-(3-iodo-1h-pyrrolo[2,3-b]pyridin-5-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CN=C2NC=C(I)C2=C1 RTZRUVMEWWPNRR-UHFFFAOYSA-N 0.000 description 1
• UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
• WHLUQAYNVOGZST-UHFFFAOYSA-N tifenamil Chemical compound C=1C=CC=CC=1C(C(=O)SCCN(CC)CC)C1=CC=CC=C1 WHLUQAYNVOGZST-UHFFFAOYSA-N 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 238000012549 training Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000007723 transport mechanism Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
• 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 238000010200 validation analysis Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 235000012431 wafers Nutrition 0.000 description 1
• 239000013585 weight reducing agent Substances 0.000 description 1
• 239000012130 whole-cell lysate Substances 0.000 description 1
• 239000009637 wintergreen oil Substances 0.000 description 1
• 229940002552 xenical Drugs 0.000 description 1