JP7549344B2 - 治療有効量の５－［［４－［２－［５－（１－ヒドロキシエチル）ピリジン－２－イル］エトキシ］フェニル］メチル］－１，３－チアゾリジン－２，４－ジオンを投与する方法 - Google Patents
治療有効量の５－［［４－［２－［５－（１－ヒドロキシエチル）ピリジン－２－イル］エトキシ］フェニル］メチル］－１，３－チアゾリジン－２，４－ジオンを投与する方法 Download PDFInfo
- Publication number
- JP7549344B2 JP7549344B2 JP2020567799A JP2020567799A JP7549344B2 JP 7549344 B2 JP7549344 B2 JP 7549344B2 JP 2020567799 A JP2020567799 A JP 2020567799A JP 2020567799 A JP2020567799 A JP 2020567799A JP 7549344 B2 JP7549344 B2 JP 7549344B2
- Authority
- JP
- Japan
- Prior art keywords
- patient
- thiazolidine
- pyridin
- hydroxyethyl
- ethoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- OXVFDZYQLGRLCD-UHFFFAOYSA-N hydroxypioglitazone Chemical compound N1=CC(C(O)C)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 OXVFDZYQLGRLCD-UHFFFAOYSA-N 0.000 title claims description 172
- 238000000034 method Methods 0.000 title claims description 166
- 150000001875 compounds Chemical class 0.000 claims description 403
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 225
- 150000003839 salts Chemical class 0.000 claims description 183
- 229940100692 oral suspension Drugs 0.000 claims description 152
- 208000035475 disorder Diseases 0.000 claims description 117
- 230000036470 plasma concentration Effects 0.000 claims description 114
- 201000010099 disease Diseases 0.000 claims description 108
- 239000000203 mixture Substances 0.000 claims description 94
- SBHOQYCDAHAMDW-UHFFFAOYSA-N 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione;hydrochloride Chemical compound Cl.N1=CC(C(O)C)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 SBHOQYCDAHAMDW-UHFFFAOYSA-N 0.000 claims description 81
- 208000012268 mitochondrial disease Diseases 0.000 claims description 48
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 36
- 230000007812 deficiency Effects 0.000 claims description 34
- 208000001992 Autosomal Dominant Optic Atrophy Diseases 0.000 claims description 32
- 208000015114 central nervous system disease Diseases 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 24
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 23
- 208000011580 syndromic disease Diseases 0.000 claims description 22
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims description 20
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 claims description 20
- 206010003591 Ataxia Diseases 0.000 claims description 18
- 208000009564 MELAS Syndrome Diseases 0.000 claims description 18
- 208000005264 motor neuron disease Diseases 0.000 claims description 18
- 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 16
- 201000000915 Chronic Progressive External Ophthalmoplegia Diseases 0.000 claims description 16
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims description 16
- 206010048804 Kearns-Sayre syndrome Diseases 0.000 claims description 16
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 16
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 16
- 230000010627 oxidative phosphorylation Effects 0.000 claims description 14
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims description 13
- 201000009028 early myoclonic encephalopathy Diseases 0.000 claims description 13
- 201000001119 neuropathy Diseases 0.000 claims description 13
- 230000007823 neuropathy Effects 0.000 claims description 13
- 208000023275 Autoimmune disease Diseases 0.000 claims description 12
- 201000006935 Becker muscular dystrophy Diseases 0.000 claims description 12
- 208000006136 Leigh Disease Diseases 0.000 claims description 12
- 208000017507 Leigh syndrome Diseases 0.000 claims description 12
- 208000001769 Multiple Acyl Coenzyme A Dehydrogenase Deficiency Diseases 0.000 claims description 12
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims description 12
- 239000000835 fiber Substances 0.000 claims description 12
- 201000011548 mitochondrial DNA depletion syndrome 4b Diseases 0.000 claims description 12
- 230000035772 mutation Effects 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 12
- 239000000725 suspension Substances 0.000 claims description 12
- 208000014844 Mitochondrial neurogastrointestinal encephalomyopathy Diseases 0.000 claims description 11
- 230000004770 neurodegeneration Effects 0.000 claims description 11
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 11
- 208000026072 Motor neurone disease Diseases 0.000 claims description 10
- 230000003412 degenerative effect Effects 0.000 claims description 10
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 10
- 239000000194 fatty acid Substances 0.000 claims description 10
- 229930195729 fatty acid Natural products 0.000 claims description 10
- 150000004665 fatty acids Chemical class 0.000 claims description 10
- 230000002757 inflammatory effect Effects 0.000 claims description 10
- 208000012902 Nervous system disease Diseases 0.000 claims description 9
- 208000006011 Stroke Diseases 0.000 claims description 9
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 8
- 208000018126 Adrenomyeloneuropathy Diseases 0.000 claims description 8
- 208000029402 Bulbospinal muscular atrophy Diseases 0.000 claims description 8
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 8
- 206010058892 Carnitine deficiency Diseases 0.000 claims description 8
- 208000027747 Kennedy disease Diseases 0.000 claims description 8
- 108700006159 Long-chain acyl-CoA dehydrogenase deficiency Proteins 0.000 claims description 8
- 208000014413 Maternally-inherited diabetes and deafness Diseases 0.000 claims description 8
- 108700000232 Medium chain acyl CoA dehydrogenase deficiency Proteins 0.000 claims description 8
- 201000002169 Mitochondrial myopathy Diseases 0.000 claims description 8
- 208000013234 Pearson syndrome Diseases 0.000 claims description 8
- 208000010366 Postpoliomyelitis syndrome Diseases 0.000 claims description 8
- 208000032319 Primary lateral sclerosis Diseases 0.000 claims description 8
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 8
- 208000006289 Rett Syndrome Diseases 0.000 claims description 8
- 206010046298 Upper motor neurone lesion Diseases 0.000 claims description 8
- 208000010796 X-linked adrenoleukodystrophy Diseases 0.000 claims description 8
- 208000029560 autism spectrum disease Diseases 0.000 claims description 8
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 8
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 claims description 8
- 201000010901 lateral sclerosis Diseases 0.000 claims description 8
- 208000036546 leukodystrophy Diseases 0.000 claims description 8
- 208000004687 long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 8
- 208000003531 maternally-inherited Leigh syndrome Diseases 0.000 claims description 8
- 208000005548 medium chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 8
- 201000002697 mitochondrial DNA depletion syndrome Diseases 0.000 claims description 8
- 230000002438 mitochondrial effect Effects 0.000 claims description 8
- 201000003645 multiple acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 8
- 201000008152 organic acidemia Diseases 0.000 claims description 8
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 claims description 8
- 201000010866 very long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 8
- 230000003612 virological effect Effects 0.000 claims description 8
- 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 claims description 7
- 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 201000006938 muscular dystrophy Diseases 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000037149 Facioscapulohumeral dystrophy Diseases 0.000 claims description 6
- 208000024412 Friedreich ataxia Diseases 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
- 230000002950 deficient Effects 0.000 claims description 6
- 208000008570 facioscapulohumeral muscular dystrophy Diseases 0.000 claims description 6
- 208000006443 lactic acidosis Diseases 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 5
- 208000033866 Rare inborn errors of metabolism Diseases 0.000 claims description 5
- 210000004556 brain Anatomy 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 230000002068 genetic effect Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 208000010543 22q11.2 deletion syndrome Diseases 0.000 claims description 4
- 201000003553 3-methylglutaconic aciduria Diseases 0.000 claims description 4
- 201000002568 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Diseases 0.000 claims description 4
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 claims description 4
- 208000004724 Ataxia neuropathy spectrum Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 201000005943 Barth syndrome Diseases 0.000 claims description 4
- 208000006304 Bethlem myopathy Diseases 0.000 claims description 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 102100027943 Carnitine O-palmitoyltransferase 1, liver isoform Human genes 0.000 claims description 4
- 101710120614 Carnitine O-palmitoyltransferase 1, liver isoform Proteins 0.000 claims description 4
- 101710108984 Carnitine O-palmitoyltransferase 1, muscle isoform Proteins 0.000 claims description 4
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 4
- 208000010354 Coenzyme Q10 deficiency Diseases 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 4
- 108010035532 Collagen Proteins 0.000 claims description 4
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 claims description 4
- 102100028675 DNA polymerase subunit gamma-2, mitochondrial Human genes 0.000 claims description 4
- 206010011891 Deafness neurosensory Diseases 0.000 claims description 4
- 101710088194 Dehydrogenase Proteins 0.000 claims description 4
- 208000000398 DiGeorge Syndrome Diseases 0.000 claims description 4
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims description 4
- 102000015782 Electron Transport Complex III Human genes 0.000 claims description 4
- 108010024882 Electron Transport Complex III Proteins 0.000 claims description 4
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 4
- 208000009889 Herpes Simplex Diseases 0.000 claims description 4
- 208000007514 Herpes zoster Diseases 0.000 claims description 4
- 101000804964 Homo sapiens DNA polymerase subunit gamma-1 Proteins 0.000 claims description 4
- 101000837415 Homo sapiens DNA polymerase subunit gamma-2, mitochondrial Proteins 0.000 claims description 4
- 101000595929 Homo sapiens POLG alternative reading frame Proteins 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 4
- 208000034800 Leukoencephalopathies Diseases 0.000 claims description 4
- 208000025121 Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome Diseases 0.000 claims description 4
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 claims description 4
- 108010027062 Long-Chain Acyl-CoA Dehydrogenase Proteins 0.000 claims description 4
- 102000018653 Long-Chain Acyl-CoA Dehydrogenase Human genes 0.000 claims description 4
- 102100021644 Long-chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 claims description 4
- 201000005505 Measles Diseases 0.000 claims description 4
- 201000009906 Meningitis Diseases 0.000 claims description 4
- 206010059521 Methylmalonic aciduria Diseases 0.000 claims description 4
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 4
- 208000016131 Mitochondrial disorder due to a defect in mitochondrial protein synthesis Diseases 0.000 claims description 4
- 208000005647 Mumps Diseases 0.000 claims description 4
- 201000002481 Myositis Diseases 0.000 claims description 4
- 208000010316 Myotonia congenita Diseases 0.000 claims description 4
- 206010068871 Myotonic dystrophy Diseases 0.000 claims description 4
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 4
- 201000011152 Pemphigus Diseases 0.000 claims description 4
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 4
- 201000005746 Pituitary adenoma Diseases 0.000 claims description 4
- 206010061538 Pituitary tumour benign Diseases 0.000 claims description 4
- 208000000474 Poliomyelitis Diseases 0.000 claims description 4
- 208000008425 Protein deficiency Diseases 0.000 claims description 4
- 208000002009 Pyruvate Dehydrogenase Complex Deficiency Disease Diseases 0.000 claims description 4
- 208000021886 Pyruvate carboxylase deficiency Diseases 0.000 claims description 4
- 206010037742 Rabies Diseases 0.000 claims description 4
- 208000009966 Sensorineural Hearing Loss Diseases 0.000 claims description 4
- 102000046669 Surf-1 Human genes 0.000 claims description 4
- 108060007963 Surf-1 Proteins 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 208000010641 Tooth disease Diseases 0.000 claims description 4
- 201000006814 Ullrich congenital muscular dystrophy Diseases 0.000 claims description 4
- 201000004810 Vascular dementia Diseases 0.000 claims description 4
- 201000003554 argininosuccinic aciduria Diseases 0.000 claims description 4
- 210000000133 brain stem Anatomy 0.000 claims description 4
- 229920001436 collagen Polymers 0.000 claims description 4
- 201000006815 congenital muscular dystrophy Diseases 0.000 claims description 4
- 201000011474 congenital myopathy Diseases 0.000 claims description 4
- 229940109239 creatinine Drugs 0.000 claims description 4
- 206010014599 encephalitis Diseases 0.000 claims description 4
- 206010015037 epilepsy Diseases 0.000 claims description 4
- 230000009395 genetic defect Effects 0.000 claims description 4
- 208000007345 glycogen storage disease Diseases 0.000 claims description 4
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 208000020658 intracerebral hemorrhage Diseases 0.000 claims description 4
- 206010025135 lupus erythematosus Diseases 0.000 claims description 4
- 201000003694 methylmalonic acidemia Diseases 0.000 claims description 4
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 claims description 4
- 208000010805 mumps infectious disease Diseases 0.000 claims description 4
- 208000018360 neuromuscular disease Diseases 0.000 claims description 4
- 108010007425 oligomycin sensitivity conferring protein Proteins 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 4
- 208000021310 pituitary gland adenoma Diseases 0.000 claims description 4
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 4
- 201000002241 progressive bulbar palsy Diseases 0.000 claims description 4
- 201000008752 progressive muscular atrophy Diseases 0.000 claims description 4
- 201000004012 propionic acidemia Diseases 0.000 claims description 4
- 201000000196 pseudobulbar palsy Diseases 0.000 claims description 4
- 230000006825 purine synthesis Effects 0.000 claims description 4
- 230000006824 pyrimidine synthesis Effects 0.000 claims description 4
- 201000006473 pyruvate decarboxylase deficiency Diseases 0.000 claims description 4
- 208000015445 pyruvate dehydrogenase deficiency Diseases 0.000 claims description 4
- 208000023504 respiratory system disease Diseases 0.000 claims description 4
- 231100000879 sensorineural hearing loss Toxicity 0.000 claims description 4
- 208000023573 sensorineural hearing loss disease Diseases 0.000 claims description 4
- 208000001392 short chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 4
- 208000017520 skin disease Diseases 0.000 claims description 4
- 210000000278 spinal cord Anatomy 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 210000001685 thyroid gland Anatomy 0.000 claims description 4
- 201000002929 Carnitine palmitoyltransferase II deficiency Diseases 0.000 claims description 3
- 206010029323 Neuromyopathy Diseases 0.000 claims description 3
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 3
- 238000009825 accumulation Methods 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 230000000626 neurodegenerative effect Effects 0.000 claims description 3
- 208000008795 neuromyelitis optica Diseases 0.000 claims description 3
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 3
- 230000002981 neuropathic effect Effects 0.000 claims description 2
- 208000035172 MERRF Diseases 0.000 claims 2
- 102100035196 POLG alternative reading frame Human genes 0.000 claims 1
- -1 1 Chemical class 0.000 description 221
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 92
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 86
- 239000000090 biomarker Substances 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 28
- 108010076365 Adiponectin Proteins 0.000 description 27
- 102100031786 Adiponectin Human genes 0.000 description 27
- 230000000694 effects Effects 0.000 description 25
- 108091007638 Mitochondrial pyruvate carriers Proteins 0.000 description 24
- 108010016731 PPAR gamma Proteins 0.000 description 23
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 22
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 20
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical class N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 15
- 238000011282 treatment Methods 0.000 description 14
- 230000003247 decreasing effect Effects 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- 101100443626 Mus musculus Dner gene Proteins 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 238000000225 bioluminescence resonance energy transfer Methods 0.000 description 11
- 239000008194 pharmaceutical composition Substances 0.000 description 11
- 229940076788 pyruvate Drugs 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 239000002775 capsule Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- 235000005911 diet Nutrition 0.000 description 8
- 230000037213 diet Effects 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 229960005095 pioglitazone Drugs 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 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 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 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 6
- 235000018102 proteins Nutrition 0.000 description 6
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 5
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 5
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 5
- 108010082126 Alanine transaminase Proteins 0.000 description 5
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 5
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 5
- 102100025031 Mitochondrial pyruvate carrier 2 Human genes 0.000 description 5
- 101710165595 Mitochondrial pyruvate carrier 2 Proteins 0.000 description 5
- 101710101698 Probable mitochondrial pyruvate carrier 2 Proteins 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000004065 mitochondrial dysfunction Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 206010019708 Hepatic steatosis Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108020005196 Mitochondrial DNA Proteins 0.000 description 4
- 102100024828 Mitochondrial pyruvate carrier 1 Human genes 0.000 description 4
- 101710165590 Mitochondrial pyruvate carrier 1 Proteins 0.000 description 4
- 108091093105 Nuclear DNA Proteins 0.000 description 4
- YHIPILPTUVMWQT-UHFFFAOYSA-N Oplophorus luciferin Chemical compound C1=CC(O)=CC=C1CC(C(N1C=C(N2)C=3C=CC(O)=CC=3)=O)=NC1=C2CC1=CC=CC=C1 YHIPILPTUVMWQT-UHFFFAOYSA-N 0.000 description 4
- 101710101695 Probable mitochondrial pyruvate carrier 1 Proteins 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 208000037765 diseases and disorders Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 210000003470 mitochondria Anatomy 0.000 description 4
- 230000036284 oxygen consumption Effects 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
- 229960004586 rosiglitazone Drugs 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 231100000240 steatosis hepatitis Toxicity 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- BIZNHCWFGNKBBZ-JLHYYAGUSA-N (e)-2-cyano-3-(1-phenylindol-3-yl)prop-2-enoic acid Chemical compound C12=CC=CC=C2C(/C=C(C(=O)O)\C#N)=CN1C1=CC=CC=C1 BIZNHCWFGNKBBZ-JLHYYAGUSA-N 0.000 description 3
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 208000027205 Congenital disease Diseases 0.000 description 3
- 102100036951 DNA polymerase subunit gamma-1 Human genes 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- 208000004930 Fatty Liver Diseases 0.000 description 3
- 102100030431 Fatty acid-binding protein, adipocyte Human genes 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- 241001559542 Hippocampus hippocampus Species 0.000 description 3
- 101001062864 Homo sapiens Fatty acid-binding protein, adipocyte Proteins 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- 206010022998 Irritability Diseases 0.000 description 3
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 102000000536 PPAR gamma Human genes 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 239000007894 caplet Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 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
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 208000010706 fatty liver disease Diseases 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 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 3
- 230000000284 resting effect Effects 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 2
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 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
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108091058560 IL8 Proteins 0.000 description 2
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 2
- 208000037273 Pathologic Processes Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 101710103228 Sodium/glucose cotransporter 2 Proteins 0.000 description 2
- 102100020888 Sodium/glucose cotransporter 2 Human genes 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000001174 ascending effect Effects 0.000 description 2
- LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 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 2
- 229960001231 choline Drugs 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000027721 electron transport chain Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 208000035474 group of disease Diseases 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 210000001700 mitochondrial membrane Anatomy 0.000 description 2
- 230000006540 mitochondrial respiration Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000009054 pathological process Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 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 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-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
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical group O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 102000003808 Adiponectin Receptors Human genes 0.000 description 1
- 108090000179 Adiponectin Receptors Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 102100028116 Amine oxidase [flavin-containing] B Human genes 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 1
- UGTJLJZQQFGTJD-UHFFFAOYSA-N Carbonylcyanide-3-chlorophenylhydrazone Chemical compound ClC1=CC=CC(NN=C(C#N)C#N)=C1 UGTJLJZQQFGTJD-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- 208000029767 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diseases 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
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
- DVJAMEIQRSHVKC-BDAKNGLRSA-N Dutogliptin Chemical compound OB(O)[C@@H]1CCCN1C(=O)CN[C@H]1CNCC1 DVJAMEIQRSHVKC-BDAKNGLRSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- ZWPRRQZNBDYKLH-VIFPVBQESA-N Gemigliptin Chemical compound C([C@@H](N)CC(=O)N1CC2=C(C(=NC(=N2)C(F)(F)F)C(F)(F)F)CC1)N1CC(F)(F)CCC1=O ZWPRRQZNBDYKLH-VIFPVBQESA-N 0.000 description 1
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 1
- 229940122459 Glutamate antagonist Drugs 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000907578 Homo sapiens Forkhead box protein M1 Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
- 108010005716 Interferon beta-1a Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 1
- 206010049940 Lipogranuloma Diseases 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 101150080551 MPC2 gene Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 206010065271 Mitochondrial neurogastrointestinal encephalopathy Diseases 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 238000013234 NASH mouse model Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 102000017946 PGC-1 Human genes 0.000 description 1
- 108700038399 PGC-1 Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 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 1
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
- 241000545067 Venus Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229960004733 albiglutide Drugs 0.000 description 1
- OGWAVGNOAMXIIM-UHFFFAOYSA-N albiglutide Chemical compound O=C(O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)CNC(=O)C(N)CC=1(N=CNC=1))CCC(=O)O)C(O)C)CC2(=CC=CC=C2))C(O)C)CO)CC(=O)O)C(C)C)CO)CO)CC3(=CC=C(O)C=C3))CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCN)CCC(=O)O)CC4(=CC=CC=C4))C(CC)C)C)CC=6(C5(=C(C=CC=C5)NC=6)))CC(C)C)C(C)C)CCCCN)CCCNC(=N)N OGWAVGNOAMXIIM-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229960001667 alogliptin Drugs 0.000 description 1
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229950009977 anagliptin Drugs 0.000 description 1
- LDXYBEHACFJIEL-HNNXBMFYSA-N anagliptin Chemical compound C=1N2N=C(C)C=C2N=CC=1C(=O)NCC(C)(C)NCC(=O)N1CCC[C@H]1C#N LDXYBEHACFJIEL-HNNXBMFYSA-N 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940125688 antiparkinson agent Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 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
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 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
- 229960001713 canagliflozin Drugs 0.000 description 1
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 230000006567 cellular energy metabolism Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960002303 citric acid monohydrate Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 229960003834 dapagliflozin Drugs 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- 229960004419 dimethyl fumarate Drugs 0.000 description 1
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229960005175 dulaglutide Drugs 0.000 description 1
- 108010005794 dulaglutide Proteins 0.000 description 1
- 229950003693 dutogliptin Drugs 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 229960000556 fingolimod Drugs 0.000 description 1
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960002458 gemigliptin Drugs 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound 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 1
- 229960004346 glimepiride Drugs 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- 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 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- 239000004220 glutamic acid Substances 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
- 150000002334 glycols Chemical class 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 229960004461 interferon beta-1a Drugs 0.000 description 1
- 238000013152 interventional procedure Methods 0.000 description 1
- 239000011872 intimate mixture Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- ODBLHEXUDAPZAU-UHFFFAOYSA-N isocitric acid Chemical compound OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 description 1
- 229960004577 laquinimod Drugs 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 229960002397 linagliptin Drugs 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- 229960001093 lixisenatide Drugs 0.000 description 1
- 108010004367 lixisenatide Proteins 0.000 description 1
- CHHXEZSCHQVSRE-UHFFFAOYSA-N lobeglitazone Chemical compound C1=CC(OC)=CC=C1OC1=CC(N(C)CCOC=2C=CC(CC3C(NC(=O)S3)=O)=CC=2)=NC=N1 CHHXEZSCHQVSRE-UHFFFAOYSA-N 0.000 description 1
- 229950007685 lobeglitazone Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 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
- 239000003921 oil Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 229950000074 omarigliptin Drugs 0.000 description 1
- MKMPWKUAHLTIBJ-ISTRZQFTSA-N omarigliptin Chemical compound C1([C@H]2OC[C@@H](C[C@@H]2N)N2CC3=CN(N=C3C2)S(=O)(=O)C)=CC(F)=CC=C1F MKMPWKUAHLTIBJ-ISTRZQFTSA-N 0.000 description 1
- 229940125395 oral insulin Drugs 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000000711 polarimetry Methods 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 108700027806 rGLP-1 Proteins 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 229960004181 riluzole Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229960004937 saxagliptin Drugs 0.000 description 1
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
- 108010033693 saxagliptin Proteins 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000013424 sirius red staining Methods 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 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
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229950007151 taspoglutide Drugs 0.000 description 1
- WRGVLTAWMNZWGT-VQSPYGJZSA-N taspoglutide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NC(C)(C)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)C(C)(C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 WRGVLTAWMNZWGT-VQSPYGJZSA-N 0.000 description 1
- 108010048573 taspoglutide Proteins 0.000 description 1
- 229950000034 teneligliptin Drugs 0.000 description 1
- WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical compound O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229950010728 trelagliptin Drugs 0.000 description 1
- IWYJYHUNXVAVAA-OAHLLOKOSA-N trelagliptin Chemical compound C=1C(F)=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 IWYJYHUNXVAVAA-OAHLLOKOSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18382398.8 | 2018-06-06 | ||
| EP18382398 | 2018-06-06 | ||
| PCT/IB2019/054743 WO2019234689A1 (en) | 2018-06-06 | 2019-06-06 | Method of administering a therapeutically effective amount of 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2021527045A JP2021527045A (ja) | 2021-10-11 |
| JP2021527045A5 JP2021527045A5 (https=) | 2022-06-14 |
| JPWO2019234689A5 JPWO2019234689A5 (https=) | 2022-06-14 |
| JP7549344B2 true JP7549344B2 (ja) | 2024-09-11 |
Family
ID=62716009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020567799A Active JP7549344B2 (ja) | 2018-06-06 | 2019-06-06 | 治療有効量の５－［［４－［２－［５－（１－ヒドロキシエチル）ピリジン－２－イル］エトキシ］フェニル］メチル］－１，３－チアゾリジン－２，４－ジオンを投与する方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20210308113A1 (https=) |
| EP (1) | EP3801516A1 (https=) |
| JP (1) | JP7549344B2 (https=) |
| KR (1) | KR20210031435A (https=) |
| CN (1) | CN112512524A (https=) |
| AU (1) | AU2019283649A1 (https=) |
| BR (1) | BR112020024917A2 (https=) |
| CA (1) | CA3102407A1 (https=) |
| CL (1) | CL2020003162A1 (https=) |
| EA (1) | EA202092953A1 (https=) |
| IL (1) | IL279183A (https=) |
| MX (1) | MX2020013181A (https=) |
| SG (1) | SG11202012045UA (https=) |
| WO (1) | WO2019234689A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130158077A1 (en) | 2011-12-19 | 2013-06-20 | Ares Trading S.A. | Pharmaceutical compositions |
| FI3801515T3 (fi) | 2018-06-06 | 2025-05-27 | Minoryx Therapeutics S L | 5-[[4-[2-[5-(1-hydroksietyyli)pyridin-2-yyli]etoksi]fenyyli]metyyli]-1,3-tiatsolidiini-2,4-dionia ja sen suoloja käytettäviksi mitokondriosairauksien hoidossa |
| EP4642456A1 (en) | 2022-12-28 | 2025-11-05 | Minoryx Therapeutics S.L. | Optimized dosing of leriglitazone |
| MX2025013233A (es) | 2023-05-09 | 2026-02-03 | Minoryx Therapeutics S L | Formas polimorficas y formulaciones de leriglitazona |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009517186A (ja) | 2005-11-29 | 2009-04-30 | チルドレンズ ホスピタル メディカル センター | 薬物選択及び投薬の最適化及び個別化 |
| JP2017511339A (ja) | 2014-04-02 | 2017-04-20 | ミノリックス セラピューティクス エセ．エレ． | 中枢神経系障害の処置における２，４−チアゾリジンジオン誘導体 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140114676A1 (en) * | 2012-10-23 | 2014-04-24 | Theranos, Inc. | Drug Monitoring and Regulation Systems and Methods |
| EP3559010B1 (en) | 2016-12-23 | 2022-06-08 | Minoryx Therapeutics S.L. | Process for preparing 5-[[4-[2-[5-(1-hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione and salts thereof |
-
2019
- 2019-06-06 BR BR112020024917-3A patent/BR112020024917A2/pt not_active Application Discontinuation
- 2019-06-06 MX MX2020013181A patent/MX2020013181A/es unknown
- 2019-06-06 AU AU2019283649A patent/AU2019283649A1/en not_active Abandoned
- 2019-06-06 EA EA202092953A patent/EA202092953A1/ru unknown
- 2019-06-06 WO PCT/IB2019/054743 patent/WO2019234689A1/en not_active Ceased
- 2019-06-06 JP JP2020567799A patent/JP7549344B2/ja active Active
- 2019-06-06 CA CA3102407A patent/CA3102407A1/en active Pending
- 2019-06-06 SG SG11202012045UA patent/SG11202012045UA/en unknown
- 2019-06-06 US US16/972,368 patent/US20210308113A1/en active Pending
- 2019-06-06 CN CN201980046617.8A patent/CN112512524A/zh active Pending
- 2019-06-06 KR KR1020207037943A patent/KR20210031435A/ko not_active Abandoned
- 2019-06-06 EP EP19742912.9A patent/EP3801516A1/en active Pending
-
2020
- 2020-12-03 IL IL279183A patent/IL279183A/en unknown
- 2020-12-04 CL CL2020003162A patent/CL2020003162A1/es unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009517186A (ja) | 2005-11-29 | 2009-04-30 | チルドレンズ ホスピタル メディカル センター | 薬物選択及び投薬の最適化及び個別化 |
| JP2017511339A (ja) | 2014-04-02 | 2017-04-20 | ミノリックス セラピューティクス エセ．エレ． | 中枢神経系障害の処置における２，４−チアゾリジンジオン誘導体 |
Non-Patent Citations (3)
| Title |
|---|
| Aliment Pharmacol Ther.，2017年，Vol.46，p.56-61 |
| Exp Clin Endocrinol Diabetes 108，2000年，Suppl 2，p.S234-S242 |
| Journal of AOAC International，2010年，Vol.93, No.3，p.876-881 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112512524A (zh) | 2021-03-16 |
| WO2019234689A1 (en) | 2019-12-12 |
| BR112020024917A2 (pt) | 2021-03-09 |
| CL2020003162A1 (es) | 2021-07-02 |
| EA202092953A1 (ru) | 2021-04-12 |
| MX2020013181A (es) | 2021-02-26 |
| IL279183A (en) | 2021-01-31 |
| AU2019283649A1 (en) | 2021-01-07 |
| CA3102407A1 (en) | 2019-12-12 |
| SG11202012045UA (en) | 2021-01-28 |
| EP3801516A1 (en) | 2021-04-14 |
| KR20210031435A (ko) | 2021-03-19 |
| JP2021527045A (ja) | 2021-10-11 |
| US20210308113A1 (en) | 2021-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240091210A1 (en) | Use of 5-[[4-[2-[5-acetylpyridin-2-yl]ethoxy]benzyl]-1,3-thiazolidine-2,4-dione and its salts | |
| JP7549344B2 (ja) | 治療有効量の５－［［４－［２－［５－（１－ヒドロキシエチル）ピリジン－２－イル］エトキシ］フェニル］メチル］－１，３－チアゾリジン－２，４－ジオンを投与する方法 | |
| US20250064791A1 (en) | 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione and its salts for use in the treatment of mitochondrial diseases | |
| EP4309738A2 (en) | Method of treating medulloblastoma with an ezh2 inhibitor | |
| US11938122B2 (en) | 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3- thiazolidine-2,4-dione for treating nonalcoholic fatty liver disease | |
| EA047277B1 (ru) | Способ введения терапевтически эффективного количества 5-[[4-[2-[5-(1-гидроксиэтил)пиридин-2-ил]этокси]фенил]метил]-1,3-тиазолидин-2,4-диона | |
| HK40049546A (en) | Method of administering a therapeutically effective amount of 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione | |
| EA047194B1 (ru) | Применение 5-[4-[2-[5-ацетилпиридин-2-ил]этокси]бензил]-1,3-тиазолидин-2,4-диона и его солей | |
| HK40042762A (en) | Use of 5-[[4-[2-[5-acetylpyridin-2-yl]ethoxy]benzyl]-1,3-thiazolidine-2,4-dione and its salts | |
| EP4642456A1 (en) | Optimized dosing of leriglitazone | |
| HK40014768A (en) | 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]ph-enyl]methyl]-1,3-thiazolidine-2,4-dione for treating nonalcoholic fatty liver disease | |
| HK40014768B (en) | 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]ph-enyl]methyl]-1,3-thiazolidine-2,4-dione for treating nonalcoholic fatty liver disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220606 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220606 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230414 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230419 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230714 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230908 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231206 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240207 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240502 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20240725 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240823 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7549344 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |