KR20220054867A - Usp30 억제제로서의 활성을 갖는 치환된 시아노피롤리딘 - Google Patents
Usp30 억제제로서의 활성을 갖는 치환된 시아노피롤리딘 Download PDFInfo
- Publication number
- KR20220054867A KR20220054867A KR1020227010882A KR20227010882A KR20220054867A KR 20220054867 A KR20220054867 A KR 20220054867A KR 1020227010882 A KR1020227010882 A KR 1020227010882A KR 20227010882 A KR20227010882 A KR 20227010882A KR 20220054867 A KR20220054867 A KR 20220054867A
- Authority
- KR
- South Korea
- Prior art keywords
- disease
- cancer
- compound
- fibrosis
- deficiency
- 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.)
- Withdrawn
Links
- 101000748132 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 30 Proteins 0.000 title abstract description 78
- 239000003112 inhibitor Substances 0.000 title abstract description 29
- 230000000694 effects Effects 0.000 title abstract description 23
- QJRYYOWARFCJQZ-UHFFFAOYSA-N pyrrolidine-1-carbonitrile Chemical class N#CN1CCCC1 QJRYYOWARFCJQZ-UHFFFAOYSA-N 0.000 title abstract description 6
- 102100040052 Ubiquitin carboxyl-terminal hydrolase 30 Human genes 0.000 title description 75
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 103
- 201000010099 disease Diseases 0.000 claims abstract description 74
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 32
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 31
- 230000004761 fibrosis Effects 0.000 claims abstract description 30
- 230000004065 mitochondrial dysfunction Effects 0.000 claims abstract description 23
- 201000011510 cancer Diseases 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims description 166
- 238000000034 method Methods 0.000 claims description 81
- 239000000203 mixture Substances 0.000 claims description 54
- 238000011282 treatment Methods 0.000 claims description 37
- -1 p-methoxybenzylcarbonyl Chemical group 0.000 claims description 36
- 210000004027 cell Anatomy 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 30
- 208000035475 disorder Diseases 0.000 claims description 28
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 26
- 208000011580 syndromic disease Diseases 0.000 claims description 26
- 208000033626 Renal failure acute Diseases 0.000 claims description 25
- 201000011040 acute kidney failure Diseases 0.000 claims description 25
- 230000003176 fibrotic effect Effects 0.000 claims description 25
- 230000002438 mitochondrial effect Effects 0.000 claims description 25
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 claims description 24
- 201000006417 multiple sclerosis Diseases 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 208000020832 chronic kidney disease Diseases 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 21
- 102000045222 parkin Human genes 0.000 claims description 21
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 18
- 210000003734 kidney Anatomy 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 17
- 230000007812 deficiency Effects 0.000 claims description 16
- 230000035772 mutation Effects 0.000 claims description 15
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 13
- 208000018737 Parkinson disease Diseases 0.000 claims description 13
- 210000000056 organ Anatomy 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 13
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 102000004169 proteins and genes Human genes 0.000 claims description 11
- 102100038376 Serine/threonine-protein kinase PINK1, mitochondrial Human genes 0.000 claims description 10
- 230000007547 defect Effects 0.000 claims description 10
- 208000017169 kidney disease Diseases 0.000 claims description 10
- 230000004770 neurodegeneration Effects 0.000 claims description 10
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 9
- 210000001519 tissue Anatomy 0.000 claims description 9
- 108020005196 Mitochondrial DNA Proteins 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 8
- 206010009944 Colon cancer Diseases 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 210000003205 muscle Anatomy 0.000 claims description 7
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 7
- 231100000241 scar Toxicity 0.000 claims description 7
- WVHBLHVSKSMWCG-ZWNOBZJWSA-N C(#N)N1C[C@@H](C[C@H]1C)NC(=O)C=1OC(=NN=1)C1=CC(=CC=C1)C#N Chemical class C(#N)N1C[C@@H](C[C@H]1C)NC(=O)C=1OC(=NN=1)C1=CC(=CC=C1)C#N WVHBLHVSKSMWCG-ZWNOBZJWSA-N 0.000 claims description 6
- 208000008955 Mucolipidoses Diseases 0.000 claims description 6
- 230000006870 function Effects 0.000 claims description 6
- 230000002068 genetic effect Effects 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 208000028867 ischemia Diseases 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 201000003694 methylmalonic acidemia Diseases 0.000 claims description 6
- 230000000750 progressive effect Effects 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- VEXLPQDEUFXMKE-ZYHUDNBSSA-N C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@H]1CN([C@@H](C1)C)C#N)OC Chemical compound C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@H]1CN([C@@H](C1)C)C#N)OC VEXLPQDEUFXMKE-ZYHUDNBSSA-N 0.000 claims description 5
- XMAIFZKISSDZOH-OLZOCXBDSA-N C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@H]1CN([C@@H](C1)COC)C#N)OC Chemical compound C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@H]1CN([C@@H](C1)COC)C#N)OC XMAIFZKISSDZOH-OLZOCXBDSA-N 0.000 claims description 5
- ZHFOZKHJYBEHCX-KGLIPLIRSA-N C(#N)N1C[C@@H](C[C@H]1COC)NC(=O)C=1OC(=NN=1)C1=CC(=CC=C1)C#N Chemical compound C(#N)N1C[C@@H](C[C@H]1COC)NC(=O)C=1OC(=NN=1)C1=CC(=CC=C1)C#N ZHFOZKHJYBEHCX-KGLIPLIRSA-N 0.000 claims description 5
- 102000008186 Collagen Human genes 0.000 claims description 5
- 108010035532 Collagen Proteins 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 229920001436 collagen Polymers 0.000 claims description 5
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 5
- 230000007423 decrease Effects 0.000 claims description 5
- 230000003111 delayed effect Effects 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 208000006443 lactic acidosis Diseases 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 102100026882 Alpha-synuclein Human genes 0.000 claims description 4
- DTBYBSDRTYBMDT-OLZOCXBDSA-N C(#N)N1C[C@@H](C[C@H]1CF)NC(=O)C=1OC(=NN=1)C1=CC(=CC=C1)C#N Chemical compound C(#N)N1C[C@@H](C[C@H]1CF)NC(=O)C=1OC(=NN=1)C1=CC(=CC=C1)C#N DTBYBSDRTYBMDT-OLZOCXBDSA-N 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010058892 Carnitine deficiency Diseases 0.000 claims description 4
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 claims description 4
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 4
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 4
- 201000002832 Lewy body dementia Diseases 0.000 claims description 4
- 201000002169 Mitochondrial myopathy Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 238000009825 accumulation Methods 0.000 claims description 4
- 108090000185 alpha-Synuclein Proteins 0.000 claims description 4
- 208000015114 central nervous system disease Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 4
- 208000015362 glutaric aciduria Diseases 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000008774 maternal effect Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 4
- 208000016505 systemic primary carnitine deficiency disease Diseases 0.000 claims description 4
- 230000008733 trauma Effects 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 206010003591 Ataxia Diseases 0.000 claims description 3
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 3
- 208000032544 Cicatrix Diseases 0.000 claims description 3
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 102100030358 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Human genes 0.000 claims description 3
- 108700006159 Long-chain acyl-CoA dehydrogenase deficiency Proteins 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 108700000232 Medium chain acyl CoA dehydrogenase deficiency Proteins 0.000 claims description 3
- 208000000149 Multiple Sulfatase Deficiency Disease Diseases 0.000 claims description 3
- 208000035032 Multiple sulfatase deficiency Diseases 0.000 claims description 3
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 claims description 3
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims description 3
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 3
- 206010038979 Retroperitoneal fibrosis Diseases 0.000 claims description 3
- 210000000601 blood cell Anatomy 0.000 claims description 3
- 229940044683 chemotherapy drug Drugs 0.000 claims description 3
- 230000003920 cognitive function Effects 0.000 claims description 3
- 230000001419 dependent effect Effects 0.000 claims description 3
- 210000002744 extracellular matrix Anatomy 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 208000004687 long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 3
- 208000005548 medium chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 208000030159 metabolic disease Diseases 0.000 claims description 3
- 208000011645 metastatic carcinoma Diseases 0.000 claims description 3
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 3
- 201000011216 nasopharynx carcinoma Diseases 0.000 claims description 3
- 201000001119 neuropathy Diseases 0.000 claims description 3
- 230000007823 neuropathy Effects 0.000 claims description 3
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 230000037387 scars Effects 0.000 claims description 3
- 230000009885 systemic effect Effects 0.000 claims description 3
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 208000012260 Accidental injury Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 201000005943 Barth syndrome Diseases 0.000 claims description 2
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 208000014644 Brain disease Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
- 108700005857 Carnitine palmitoyl transferase 1A deficiency Proteins 0.000 claims description 2
- 208000005359 Carnitine palmitoyl transferase 1A deficiency Diseases 0.000 claims description 2
- 108700005858 Carnitine palmitoyl transferase 2 deficiency Proteins 0.000 claims description 2
- 201000002929 Carnitine palmitoyltransferase II deficiency Diseases 0.000 claims description 2
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 2
- 208000010354 Coenzyme Q10 deficiency Diseases 0.000 claims description 2
- 208000021075 Creatine deficiency syndrome Diseases 0.000 claims description 2
- 206010011878 Deafness Diseases 0.000 claims description 2
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims description 2
- 102000015782 Electron Transport Complex III Human genes 0.000 claims description 2
- 108010024882 Electron Transport Complex III Proteins 0.000 claims description 2
- 208000032274 Encephalopathy Diseases 0.000 claims description 2
- 208000009796 Gangliosidoses Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 101000804964 Homo sapiens DNA polymerase subunit gamma-1 Proteins 0.000 claims description 2
- 101000997662 Homo sapiens Lysosomal acid glucosylceramidase Proteins 0.000 claims description 2
- 101000595929 Homo sapiens POLG alternative reading frame Proteins 0.000 claims description 2
- 101710150008 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Proteins 0.000 claims description 2
- 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 claims description 2
- 208000002260 Keloid Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 claims description 2
- 206010050029 Mitochondrial cytopathy Diseases 0.000 claims description 2
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 claims description 2
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010033799 Paralysis Diseases 0.000 claims description 2
- 208000013234 Pearson syndrome Diseases 0.000 claims description 2
- 206010034665 Peritoneal fibrosis Diseases 0.000 claims description 2
- 208000020547 Peroxisomal disease Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000028017 Psychotic disease Diseases 0.000 claims description 2
- 208000002009 Pyruvate Dehydrogenase Complex Deficiency Disease Diseases 0.000 claims description 2
- 208000021886 Pyruvate carboxylase deficiency Diseases 0.000 claims description 2
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 206010039710 Scleroderma Diseases 0.000 claims description 2
- 208000034189 Sclerosis Diseases 0.000 claims description 2
- 201000010001 Silicosis Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 2
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 2
- 206010057644 Testis cancer Diseases 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 230000005775 apoptotic pathway Effects 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 201000009267 bronchiectasis Diseases 0.000 claims description 2
- 201000004010 carnitine palmitoyltransferase I deficiency Diseases 0.000 claims description 2
- 201000008609 cerebral creatine deficiency syndrome Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 230000001054 cortical effect Effects 0.000 claims description 2
- 231100000895 deafness Toxicity 0.000 claims description 2
- 230000007850 degeneration Effects 0.000 claims description 2
- 230000006806 disease prevention Effects 0.000 claims description 2
- 201000009028 early myoclonic encephalopathy Diseases 0.000 claims description 2
- 230000000893 fibroproliferative effect Effects 0.000 claims description 2
- 201000006440 gangliosidosis Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 208000016354 hearing loss disease Diseases 0.000 claims description 2
- 206010020718 hyperplasia Diseases 0.000 claims description 2
- 230000001969 hypertrophic effect Effects 0.000 claims description 2
- 230000028993 immune response Effects 0.000 claims description 2
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims description 2
- 210000001117 keloid Anatomy 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 231100000518 lethal Toxicity 0.000 claims description 2
- 230000001665 lethal effect Effects 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 208000031225 myocardial ischemia Diseases 0.000 claims description 2
- 230000009826 neoplastic cell growth Effects 0.000 claims description 2
- 230000002232 neuromuscular Effects 0.000 claims description 2
- 108010007425 oligomycin sensitivity conferring protein Proteins 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 201000006473 pyruvate decarboxylase deficiency Diseases 0.000 claims description 2
- 208000015445 pyruvate dehydrogenase deficiency Diseases 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 201000000306 sarcoidosis Diseases 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 210000002807 slow-twitch muscle fiber Anatomy 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 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 description 2
- 201000003120 testicular cancer Diseases 0.000 claims description 2
- 230000017423 tissue regeneration Effects 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 208000009270 3-hydroxyacyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 102000051485 Bcl-2 family Human genes 0.000 claims 1
- 108700038897 Bcl-2 family Proteins 0.000 claims 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
- 208000011518 Danon disease Diseases 0.000 claims 1
- 208000001708 Dupuytren contracture Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 208000001500 Glycogen Storage Disease Type IIb Diseases 0.000 claims 1
- 208000035148 Glycogen storage disease due to LAMP-2 deficiency Diseases 0.000 claims 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims 1
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims 1
- 101000605835 Homo sapiens Serine/threonine-protein kinase PINK1, mitochondrial Proteins 0.000 claims 1
- 206010048804 Kearns-Sayre syndrome Diseases 0.000 claims 1
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 claims 1
- 208000018142 Leiomyosarcoma Diseases 0.000 claims 1
- 102000009784 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Human genes 0.000 claims 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 206010029888 Obliterative bronchiolitis Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 102100035196 POLG alternative reading frame Human genes 0.000 claims 1
- 208000032383 Soft tissue cancer Diseases 0.000 claims 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims 1
- 201000003848 bronchiolitis obliterans Diseases 0.000 claims 1
- 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 claims 1
- 230000001667 episodic effect Effects 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 210000002950 fibroblast Anatomy 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 206010024627 liposarcoma Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 208000003531 maternally-inherited Leigh syndrome Diseases 0.000 claims 1
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 claims 1
- 201000010866 very long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- 230000002829 reductive effect Effects 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 230000021125 mitochondrion degradation Effects 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000003556 assay Methods 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- 238000000338 in vitro Methods 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 102000001477 Deubiquitinating Enzymes Human genes 0.000 description 13
- 108010093668 Deubiquitinating Enzymes Proteins 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 238000010798 ubiquitination Methods 0.000 description 10
- 101710168567 Serine/threonine-protein kinase PINK1, mitochondrial Proteins 0.000 description 9
- 210000003470 mitochondria Anatomy 0.000 description 9
- 230000003389 potentiating effect Effects 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 238000001262 western blot Methods 0.000 description 9
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- 102000005600 Cathepsins Human genes 0.000 description 8
- 108010084457 Cathepsins Proteins 0.000 description 8
- 108090000848 Ubiquitin Proteins 0.000 description 8
- 102000044159 Ubiquitin Human genes 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 210000001035 gastrointestinal tract Anatomy 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 230000034512 ubiquitination Effects 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 108010005656 Ubiquitin Thiolesterase Proteins 0.000 description 7
- 102000005918 Ubiquitin Thiolesterase Human genes 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 230000033228 biological regulation Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000002503 metabolic effect Effects 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 101000807540 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 25 Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 102100037179 Ubiquitin carboxyl-terminal hydrolase 25 Human genes 0.000 description 6
- CWGJBBRZFIPXNZ-UHFFFAOYSA-N [C-]#N.Br Chemical compound [C-]#N.Br CWGJBBRZFIPXNZ-UHFFFAOYSA-N 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- VTRYJVJUYVXCPY-UHFFFAOYSA-N ethyl 5-(3-cyanophenyl)-1,3,4-oxadiazole-2-carboxylate Chemical compound CCOC(=O)C1=NN=C(O1)C1=CC(=CC=C1)C#N VTRYJVJUYVXCPY-UHFFFAOYSA-N 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 238000011321 prophylaxis Methods 0.000 description 6
- 201000002793 renal fibrosis Diseases 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 108010006654 Bleomycin Proteins 0.000 description 5
- 101000798951 Homo sapiens Mitochondrial import receptor subunit TOM20 homolog Proteins 0.000 description 5
- 101000607872 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 21 Proteins 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 102100034007 Mitochondrial import receptor subunit TOM20 homolog Human genes 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 229960001561 bleomycin Drugs 0.000 description 5
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 5
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 230000000155 isotopic effect Effects 0.000 description 5
- 210000005229 liver cell Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 230000036542 oxidative stress Effects 0.000 description 5
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 5
- 229960003073 pirfenidone Drugs 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- FFCXLXHOUNLHOX-UHFFFAOYSA-N C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)OCC)OC Chemical compound C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)OCC)OC FFCXLXHOUNLHOX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 101001126977 Homo sapiens Methylmalonyl-CoA mutase, mitochondrial Proteins 0.000 description 4
- 101000748141 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 32 Proteins 0.000 description 4
- 102100030979 Methylmalonyl-CoA mutase, mitochondrial Human genes 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 102100040050 Ubiquitin carboxyl-terminal hydrolase 32 Human genes 0.000 description 4
- 102100040048 Ubiquitin carboxyl-terminal hydrolase 35 Human genes 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 230000004900 autophagic degradation Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 208000012268 mitochondrial disease Diseases 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 4
- 229960004378 nintedanib Drugs 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000003642 reactive oxygen metabolite Substances 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- KYKPMNVLZRQRHZ-UHFFFAOYSA-N 3-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC(C#N)=C1 KYKPMNVLZRQRHZ-UHFFFAOYSA-N 0.000 description 3
- QXNXTUKGVJNVRV-UHFFFAOYSA-N C(#N)C=1C=CC(=C(C(=O)NN)C=1)OC Chemical compound C(#N)C=1C=CC(=C(C(=O)NN)C=1)OC QXNXTUKGVJNVRV-UHFFFAOYSA-N 0.000 description 3
- LHWLCRBKYAXNMT-UHFFFAOYSA-N C(#N)C=1C=CC(=C(C(=O)NNC(C(=O)OCC)=O)C=1)OC Chemical compound C(#N)C=1C=CC(=C(C(=O)NNC(C(=O)OCC)=O)C=1)OC LHWLCRBKYAXNMT-UHFFFAOYSA-N 0.000 description 3
- 102100022207 E3 ubiquitin-protein ligase parkin Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000809243 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 10 Proteins 0.000 description 3
- 101000841471 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 15 Proteins 0.000 description 3
- 101000939517 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 2 Proteins 0.000 description 3
- 101000807524 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 22 Proteins 0.000 description 3
- 101000939467 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 28 Proteins 0.000 description 3
- 101000748159 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 35 Proteins 0.000 description 3
- 101000759984 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 46 Proteins 0.000 description 3
- 101000809126 Homo sapiens Ubiquitin carboxyl-terminal hydrolase isozyme L5 Proteins 0.000 description 3
- 206010023421 Kidney fibrosis Diseases 0.000 description 3
- 108010058682 Mitochondrial Proteins Proteins 0.000 description 3
- 102000006404 Mitochondrial Proteins Human genes 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010061481 Renal injury Diseases 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 102100029164 Ubiquitin carboxyl-terminal hydrolase 15 Human genes 0.000 description 3
- 102100029643 Ubiquitin carboxyl-terminal hydrolase 2 Human genes 0.000 description 3
- 102100037184 Ubiquitin carboxyl-terminal hydrolase 22 Human genes 0.000 description 3
- 102100029821 Ubiquitin carboxyl-terminal hydrolase 28 Human genes 0.000 description 3
- 102100025025 Ubiquitin carboxyl-terminal hydrolase 46 Human genes 0.000 description 3
- 102100038443 Ubiquitin carboxyl-terminal hydrolase isozyme L5 Human genes 0.000 description 3
- 102100039414 WD repeat-containing protein 48 Human genes 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 3
- 230000005779 cell damage Effects 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- YYMYHIYVACBPBF-UHFFFAOYSA-N ethyl 2-[2-(3-cyanobenzoyl)hydrazinyl]-2-oxoacetate Chemical compound C(#N)C=1C=C(C(=O)NNC(C(=O)OCC)=O)C=CC=1 YYMYHIYVACBPBF-UHFFFAOYSA-N 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 230000003907 kidney function Effects 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 239000012669 liquid formulation Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- PIXOBZFOAGWQGO-UHFFFAOYSA-N methyl 5-cyano-2-methoxybenzoate Chemical compound COC(=O)C1=CC(C#N)=CC=C1OC PIXOBZFOAGWQGO-UHFFFAOYSA-N 0.000 description 3
- 210000001700 mitochondrial membrane Anatomy 0.000 description 3
- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 239000008177 pharmaceutical agent Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 210000005084 renal tissue Anatomy 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 230000001839 systemic circulation 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
- 101150042041 wdr48 gene Proteins 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
- GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 2
- QHWZMDRKTYTPEE-UHFFFAOYSA-N 3-bromo-4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1Br QHWZMDRKTYTPEE-UHFFFAOYSA-N 0.000 description 2
- JYCQQPHGFMYQCF-UHFFFAOYSA-N 4-tert-Octylphenol monoethoxylate Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCO)C=C1 JYCQQPHGFMYQCF-UHFFFAOYSA-N 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- HPLNQCPCUACXLM-PGUFJCEWSA-N ABT-737 Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(=O)(=O)NC(=O)C=1C=CC(=CC=1)N1CCN(CC=2C(=CC=CC=2)C=2C=CC(Cl)=CC=2)CC1)[N+]([O-])=O)SC1=CC=CC=C1 HPLNQCPCUACXLM-PGUFJCEWSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 102000006378 Catechol O-methyltransferase Human genes 0.000 description 2
- 108020002739 Catechol O-methyltransferase Proteins 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 2
- 101000809261 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 11 Proteins 0.000 description 2
- 101000644815 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 16 Proteins 0.000 description 2
- 101000809257 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 4 Proteins 0.000 description 2
- 101000841466 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 8 Proteins 0.000 description 2
- 101001052436 Homo sapiens Ubiquitin carboxyl-terminal hydrolase MINDY-2 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 108010027062 Long-Chain Acyl-CoA Dehydrogenase Proteins 0.000 description 2
- 102000018653 Long-Chain Acyl-CoA Dehydrogenase Human genes 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 206010048302 Tubulointerstitial nephritis Diseases 0.000 description 2
- 101150020913 USP7 gene Proteins 0.000 description 2
- 102100038462 Ubiquitin carboxyl-terminal hydrolase 11 Human genes 0.000 description 2
- 102100039918 Ubiquitin carboxyl-terminal hydrolase 21 Human genes 0.000 description 2
- 102100038463 Ubiquitin carboxyl-terminal hydrolase 4 Human genes 0.000 description 2
- 102100021013 Ubiquitin carboxyl-terminal hydrolase 7 Human genes 0.000 description 2
- 102100029088 Ubiquitin carboxyl-terminal hydrolase 8 Human genes 0.000 description 2
- 102100024198 Ubiquitin carboxyl-terminal hydrolase MINDY-2 Human genes 0.000 description 2
- 108700011958 Ubiquitin-Specific Peptidase 7 Proteins 0.000 description 2
- 229940126752 Ubiquitin-specific protease 7 inhibitor Drugs 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- JFRKIFOHHPKORS-UHFFFAOYSA-N [C].N1CCCC1 Chemical group [C].N1CCCC1 JFRKIFOHHPKORS-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 238000010256 biochemical assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229960001467 bortezomib Drugs 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 201000000523 end stage renal failure Diseases 0.000 description 2
- OWZFULPEVHKEKS-UHFFFAOYSA-N ethyl 2-chloro-2-oxoacetate Chemical compound CCOC(=O)C(Cl)=O OWZFULPEVHKEKS-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000005865 ionizing radiation Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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
- XPBHWSMZTSSEJE-UHFFFAOYSA-N methyl 3-cyanobenzoate Chemical compound COC(=O)C1=CC=CC(C#N)=C1 XPBHWSMZTSSEJE-UHFFFAOYSA-N 0.000 description 2
- 239000008185 minitablet Substances 0.000 description 2
- 230000008437 mitochondrial biogenesis Effects 0.000 description 2
- 230000007659 motor function Effects 0.000 description 2
- 230000003505 mutagenic effect Effects 0.000 description 2
- 210000000651 myofibroblast Anatomy 0.000 description 2
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 description 1
- MNULEGDCPYONBU-DJRUDOHVSA-N (1s,4r,5z,5'r,6'r,7e,10s,11r,12s,14r,15s,18r,19r,20s,21e,26r,27s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@H]1CC[C@H](\C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)C(C)C(=O)[C@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)OC([C@H]2C)C1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-DJRUDOHVSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- CVCLJVVBHYOXDC-IAZSKANUSA-N (2z)-2-[(5z)-5-[(3,5-dimethyl-1h-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole Chemical compound COC1=C\C(=C/2N=C3C=CC=CC3=C\2)N\C1=C/C=1NC(C)=CC=1C CVCLJVVBHYOXDC-IAZSKANUSA-N 0.000 description 1
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 1
- MNULEGDCPYONBU-YNZHUHFTSA-N (4Z,18Z,20Z)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC1C(C2C)OC(=O)\C=C/C(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)C\C=C/C=C\C(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-YNZHUHFTSA-N 0.000 description 1
- MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical class C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 1
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- GUDJFFQZIISQJB-UHFFFAOYSA-N 4-cyano-5-(3,5-dichloropyridin-4-yl)sulfanyl-n-(4-methylsulfonylphenyl)thiophene-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC(=O)C(S1)=CC(C#N)=C1SC1=C(Cl)C=NC=C1Cl GUDJFFQZIISQJB-UHFFFAOYSA-N 0.000 description 1
- MNULEGDCPYONBU-UHFFFAOYSA-N 4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 description 1
- KSPDSMOWMQFPBL-UHFFFAOYSA-N 5-fluoropyrimidine Chemical compound FC1=CN=CN=C1 KSPDSMOWMQFPBL-UHFFFAOYSA-N 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
- 102100025261 AMSH-like protease Human genes 0.000 description 1
- 101710195537 AMSH-like protease Proteins 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 238000010953 Ames test Methods 0.000 description 1
- 231100000039 Ames test Toxicity 0.000 description 1
- 108700023418 Amidases Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- UIFFUZWRFRDZJC-UHFFFAOYSA-N Antimycin A1 Natural products CC1OC(=O)C(CCCCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-UHFFFAOYSA-N 0.000 description 1
- NQWZLRAORXLWDN-UHFFFAOYSA-N Antimycin-A Natural products CCCCCCC(=O)OC1C(C)OC(=O)C(NC(=O)c2ccc(NC=O)cc2O)C(C)OC(=O)C1CCCC NQWZLRAORXLWDN-UHFFFAOYSA-N 0.000 description 1
- 101100261173 Arabidopsis thaliana TPS7 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- NUBDJMYTOUQORS-DNVCBOLYSA-N C(#N)C=1C=C(C=CC=1)C1=CC(=NC=C1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C Chemical compound C(#N)C=1C=C(C=CC=1)C1=CC(=NC=C1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C NUBDJMYTOUQORS-DNVCBOLYSA-N 0.000 description 1
- DFPNEFVNMSGJAN-IUODEOHRSA-N C(#N)C=1C=C(C=CC=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C Chemical compound C(#N)C=1C=C(C=CC=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)C DFPNEFVNMSGJAN-IUODEOHRSA-N 0.000 description 1
- UWHKILLQDSWULJ-CABCVRRESA-N C(#N)C=1C=C(C=CC=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)CF Chemical compound C(#N)C=1C=C(C=CC=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)CF UWHKILLQDSWULJ-CABCVRRESA-N 0.000 description 1
- UVOFWCUAPJYJSE-CVEARBPZSA-N C(#N)C=1C=C(C=CC=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)COC Chemical compound C(#N)C=1C=C(C=CC=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)COC UVOFWCUAPJYJSE-CVEARBPZSA-N 0.000 description 1
- VCHFLCHWBAIESG-CABCVRRESA-N C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)COC)OC Chemical compound C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@@H]1C[C@H](N(C1)C(=O)OC(C)(C)C)COC)OC VCHFLCHWBAIESG-CABCVRRESA-N 0.000 description 1
- NJDRSIHZMWAXCD-MWLCHTKSSA-N C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@H]1CN[C@@H](C1)C)OC Chemical class C(#N)C=1C=CC(=C(C=1)C1=NN=C(O1)C(=O)N[C@H]1CN[C@@H](C1)C)OC NJDRSIHZMWAXCD-MWLCHTKSSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 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
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000003902 Cathepsin C Human genes 0.000 description 1
- 108090000267 Cathepsin C Proteins 0.000 description 1
- 108090000624 Cathepsin L Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010011469 Crying Diseases 0.000 description 1
- 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 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000007035 DNA breakage Effects 0.000 description 1
- 102100036951 DNA polymerase subunit gamma-1 Human genes 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 102100040561 Deubiquitinase OTUD6B Human genes 0.000 description 1
- 108010086291 Deubiquitinating Enzyme CYLD Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
- 101000957747 Drosophila melanogaster Transmembrane GTPase Marf Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010072268 Drug-induced liver injury Diseases 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 229910016860 FaSSIF Inorganic materials 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 101000613797 Homo sapiens Deubiquitinase OTUD6B Proteins 0.000 description 1
- 101001095815 Homo sapiens E3 ubiquitin-protein ligase RING2 Proteins 0.000 description 1
- 101001083553 Homo sapiens Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Proteins 0.000 description 1
- 101000994432 Homo sapiens Josephin-1 Proteins 0.000 description 1
- 101000994428 Homo sapiens Josephin-2 Proteins 0.000 description 1
- 101000966742 Homo sapiens Leucine-rich PPR motif-containing protein, mitochondrial Proteins 0.000 description 1
- 101001057193 Homo sapiens Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 Proteins 0.000 description 1
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 1
- 101000721382 Homo sapiens OTU domain-containing protein 3 Proteins 0.000 description 1
- 101000721386 Homo sapiens OTU domain-containing protein 5 Proteins 0.000 description 1
- 101000613787 Homo sapiens OTU domain-containing protein 6A Proteins 0.000 description 1
- 101000613798 Homo sapiens OTU domain-containing protein 7B Proteins 0.000 description 1
- 101100518559 Homo sapiens OTUB1 gene Proteins 0.000 description 1
- 101000808592 Homo sapiens Probable ubiquitin carboxyl-terminal hydrolase FAF-X Proteins 0.000 description 1
- 101000684497 Homo sapiens Sentrin-specific protease 2 Proteins 0.000 description 1
- 101000684514 Homo sapiens Sentrin-specific protease 6 Proteins 0.000 description 1
- 101000607909 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 1 Proteins 0.000 description 1
- 101000760210 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 12 Proteins 0.000 description 1
- 101000760229 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 13 Proteins 0.000 description 1
- 101000841477 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 14 Proteins 0.000 description 1
- 101000644843 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 19 Proteins 0.000 description 1
- 101000607865 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 20 Proteins 0.000 description 1
- 101000807541 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 24 Proteins 0.000 description 1
- 101000748161 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 34 Proteins 0.000 description 1
- 101000671819 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 36 Proteins 0.000 description 1
- 101000760243 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 45 Proteins 0.000 description 1
- 101000759994 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 47 Proteins 0.000 description 1
- 101000759988 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 48 Proteins 0.000 description 1
- 101000643890 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 5 Proteins 0.000 description 1
- 101000643895 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 6 Proteins 0.000 description 1
- 101000740048 Homo sapiens Ubiquitin carboxyl-terminal hydrolase BAP1 Proteins 0.000 description 1
- 101000759918 Homo sapiens Ubiquitin carboxyl-terminal hydrolase isozyme L3 Proteins 0.000 description 1
- 101001121442 Homo sapiens Ubiquitin thioesterase OTU1 Proteins 0.000 description 1
- 101000720948 Homo sapiens Ubiquitin thioesterase OTUB2 Proteins 0.000 description 1
- 101000723423 Homo sapiens Ubiquitin thioesterase ZRANB1 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020524 Hydronephrosis Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 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 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 102100032732 Josephin-1 Human genes 0.000 description 1
- 102100032731 Josephin-2 Human genes 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
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-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
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- 101000740049 Latilactobacillus curvatus Bioactive peptide 1 Proteins 0.000 description 1
- 102100040589 Leucine-rich PPR motif-containing protein, mitochondrial Human genes 0.000 description 1
- 102100032693 Leucine-rich repeat serine/threonine-protein kinase 2 Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010072930 Mucolipidosis type IV Diseases 0.000 description 1
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 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
- 150000001204 N-oxides Chemical class 0.000 description 1
- JLEBZPBDRKPWTD-TURQNECASA-O N-ribosylnicotinamide Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1 JLEBZPBDRKPWTD-TURQNECASA-O 0.000 description 1
- IPKYBSNQDSPYFW-UHFFFAOYSA-N NC(C1=NN=C(C2=CC(C#N)=CC=C2)O1)=O Chemical compound NC(C1=NN=C(C2=CC(C#N)=CC=C2)O1)=O IPKYBSNQDSPYFW-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108091093105 Nuclear DNA Proteins 0.000 description 1
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 102100025196 OTU domain-containing protein 3 Human genes 0.000 description 1
- 102100025194 OTU domain-containing protein 5 Human genes 0.000 description 1
- 102100040564 OTU domain-containing protein 6A Human genes 0.000 description 1
- 102100040562 OTU domain-containing protein 7B Human genes 0.000 description 1
- 101150115940 OTU1 gene Proteins 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 101710116435 Outer membrane protein Proteins 0.000 description 1
- 102000004020 Oxygenases Human genes 0.000 description 1
- 108090000417 Oxygenases Proteins 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 101150100341 PEX2 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 101150118397 Pex5l gene Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 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
- 102100038603 Probable ubiquitin carboxyl-terminal hydrolase FAF-X Human genes 0.000 description 1
- 102100026534 Procathepsin L Human genes 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 244000088415 Raphanus sativus Species 0.000 description 1
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 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
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102100023646 Sentrin-specific protease 2 Human genes 0.000 description 1
- 102100023713 Sentrin-specific protease 6 Human genes 0.000 description 1
- 206010050207 Skin fibrosis Diseases 0.000 description 1
- 239000004115 Sodium Silicate Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102100040347 TAR DNA-binding protein 43 Human genes 0.000 description 1
- 101710150875 TAR DNA-binding protein 43 Proteins 0.000 description 1
- 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 1
- 229940123237 Taxane Drugs 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- 208000018452 Torsade de pointes Diseases 0.000 description 1
- 208000002363 Torsades de Pointes Diseases 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 1
- 108091034406 USP family Proteins 0.000 description 1
- 102100039865 Ubiquitin carboxyl-terminal hydrolase 1 Human genes 0.000 description 1
- 102100024662 Ubiquitin carboxyl-terminal hydrolase 12 Human genes 0.000 description 1
- 102100024720 Ubiquitin carboxyl-terminal hydrolase 13 Human genes 0.000 description 1
- 102100029163 Ubiquitin carboxyl-terminal hydrolase 14 Human genes 0.000 description 1
- 102100020728 Ubiquitin carboxyl-terminal hydrolase 19 Human genes 0.000 description 1
- 102100039920 Ubiquitin carboxyl-terminal hydrolase 20 Human genes 0.000 description 1
- 102100037176 Ubiquitin carboxyl-terminal hydrolase 24 Human genes 0.000 description 1
- 102100040109 Ubiquitin carboxyl-terminal hydrolase 36 Human genes 0.000 description 1
- 102100024718 Ubiquitin carboxyl-terminal hydrolase 45 Human genes 0.000 description 1
- 102100025029 Ubiquitin carboxyl-terminal hydrolase 47 Human genes 0.000 description 1
- 102100025023 Ubiquitin carboxyl-terminal hydrolase 48 Human genes 0.000 description 1
- 102100021017 Ubiquitin carboxyl-terminal hydrolase 5 Human genes 0.000 description 1
- 102100021015 Ubiquitin carboxyl-terminal hydrolase 6 Human genes 0.000 description 1
- 102100037587 Ubiquitin carboxyl-terminal hydrolase BAP1 Human genes 0.000 description 1
- 102100024250 Ubiquitin carboxyl-terminal hydrolase CYLD Human genes 0.000 description 1
- 102100025040 Ubiquitin carboxyl-terminal hydrolase isozyme L3 Human genes 0.000 description 1
- 102100026369 Ubiquitin thioesterase OTU1 Human genes 0.000 description 1
- 102100040461 Ubiquitin thioesterase OTUB1 Human genes 0.000 description 1
- 102100025914 Ubiquitin thioesterase OTUB2 Human genes 0.000 description 1
- 102100027846 Ubiquitin thioesterase ZRANB1 Human genes 0.000 description 1
- 108010066496 Ubiquitin-Specific Proteases Proteins 0.000 description 1
- 102000018390 Ubiquitin-Specific Proteases Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000004608 Ureteral Obstruction Diseases 0.000 description 1
- 108010067973 Valinomycin Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 208000019291 X-linked disease Diseases 0.000 description 1
- GLQOALGKMKUSBF-UHFFFAOYSA-N [amino(diphenyl)silyl]benzene Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(N)C1=CC=CC=C1 GLQOALGKMKUSBF-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000037328 acute stress Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000001943 adrenal medulla Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 101150045355 akt1 gene Proteins 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 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
- 102000005922 amidase Human genes 0.000 description 1
- 239000003460 aneugen Substances 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002547 anomalous effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000009949 anti-apoptotic pathway Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- UIFFUZWRFRDZJC-SBOOETFBSA-N antimycin A Chemical compound C[C@H]1OC(=O)[C@H](CCCCCC)[C@@H](OC(=O)CC(C)C)[C@H](C)OC(=O)[C@H]1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-SBOOETFBSA-N 0.000 description 1
- PVEVXUMVNWSNIG-UHFFFAOYSA-N antimycin A3 Natural products CC1OC(=O)C(CCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O PVEVXUMVNWSNIG-UHFFFAOYSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
- 230000004642 autophagic pathway Effects 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- JMLFOZVZGFQYOT-UHFFFAOYSA-N butanedioic acid;sulfuric acid Chemical compound OS(O)(=O)=O.OC(=O)CCC(O)=O JMLFOZVZGFQYOT-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000015111 chews Nutrition 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 231100000244 chromosomal damage Toxicity 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 239000003280 clastogen Substances 0.000 description 1
- 231100000506 clastogen Toxicity 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- 229960003120 clonazepam Drugs 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- FCFNRCROJUBPLU-UHFFFAOYSA-N compound M126 Natural products CC(C)C1NC(=O)C(C)OC(=O)C(C(C)C)NC(=O)C(C(C)C)OC(=O)C(C(C)C)NC(=O)C(C)OC(=O)C(C(C)C)NC(=O)C(C(C)C)OC(=O)C(C(C)C)NC(=O)C(C)OC(=O)C(C(C)C)NC(=O)C(C(C)C)OC1=O FCFNRCROJUBPLU-UHFFFAOYSA-N 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000009504 deubiquitination Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 229950010286 diolamine Drugs 0.000 description 1
- 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 1
- 238000007907 direct compression Methods 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 239000002308 endothelin receptor antagonist Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 description 1
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 description 1
- 238000012395 formulation development Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 231100000024 genotoxic Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 208000014188 hereditary optic neuropathy Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical class 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007915 intraurethral administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000002555 ionophore Substances 0.000 description 1
- 230000000236 ionophoric effect Effects 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 208000037806 kidney injury Diseases 0.000 description 1
- 229940116871 l-lactate Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 230000006674 lysosomal degradation Effects 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 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
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 230000003818 metabolic dysfunction Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 238000006241 metabolic reaction Methods 0.000 description 1
- GPKUICFDWYEPTK-UHFFFAOYSA-N methoxycyclohexatriene Chemical compound COC1=CC=C=C[CH]1 GPKUICFDWYEPTK-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 231100001069 micronucleus induction Toxicity 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000006705 mitochondrial oxidative phosphorylation Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 210000000479 mitotic spindle apparatus Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 231100000243 mutagenic effect Toxicity 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- JLYAXFNOILIKPP-KXQOOQHDSA-N navitoclax Chemical compound C([C@@H](NC1=CC=C(C=C1S(=O)(=O)C(F)(F)F)S(=O)(=O)NC(=O)C1=CC=C(C=C1)N1CCN(CC1)CC1=C(CCC(C1)(C)C)C=1C=CC(Cl)=CC=1)CSC=1C=CC=CC=1)CN1CCOCC1 JLYAXFNOILIKPP-KXQOOQHDSA-N 0.000 description 1
- 229950004847 navitoclax Drugs 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 235000020956 nicotinamide riboside Nutrition 0.000 description 1
- 239000011618 nicotinamide riboside Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 229950006584 obatoclax Drugs 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 201000002674 obstructive nephropathy Diseases 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- UYDLBVPAAFVANX-UHFFFAOYSA-N octylphenoxy polyethoxyethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCO)C=C1 UYDLBVPAAFVANX-UHFFFAOYSA-N 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 229950004864 olamine Drugs 0.000 description 1
- 229960000572 olaparib Drugs 0.000 description 1
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 description 1
- 229930191479 oligomycin Natural products 0.000 description 1
- MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229940023569 palmate Drugs 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 230000002206 pro-fibrotic effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 229960004181 riluzole Drugs 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 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
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007921 solubility assay Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 229960005333 tetrabenazine Drugs 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 125000005490 tosylate group Chemical class 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000004926 tubular epithelial cell Anatomy 0.000 description 1
- 208000037999 tubulointerstitial fibrosis Diseases 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 101150005573 uvrA gene Proteins 0.000 description 1
- FCFNRCROJUBPLU-DNDCDFAISA-N valinomycin Chemical compound CC(C)[C@@H]1NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC(=O)[C@H](C(C)C)NC(=O)[C@H](C)OC(=O)[C@@H](C(C)C)NC(=O)[C@@H](C(C)C)OC1=O FCFNRCROJUBPLU-DNDCDFAISA-N 0.000 description 1
- 229940099039 velcade Drugs 0.000 description 1
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 description 1
- 229960001183 venetoclax Drugs 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1912674.7A GB201912674D0 (en) | 2019-09-04 | 2019-09-04 | Novel compounds |
| GB1912674.7 | 2019-09-04 | ||
| PCT/EP2020/074540 WO2021043870A1 (en) | 2019-09-04 | 2020-09-03 | Substituted cyanopyrrolidines with activity as usp30 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20220054867A true KR20220054867A (ko) | 2022-05-03 |
Family
ID=68207049
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020227010882A Withdrawn KR20220054867A (ko) | 2019-09-04 | 2020-09-03 | Usp30 억제제로서의 활성을 갖는 치환된 시아노피롤리딘 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20220315572A1 (https=) |
| EP (1) | EP4025573B9 (https=) |
| JP (1) | JP2022546717A (https=) |
| KR (1) | KR20220054867A (https=) |
| CN (1) | CN114341133B (https=) |
| AU (1) | AU2020340527A1 (https=) |
| BR (1) | BR112022003527A2 (https=) |
| CA (1) | CA3146040A1 (https=) |
| CO (1) | CO2022003608A2 (https=) |
| GB (1) | GB201912674D0 (https=) |
| IL (1) | IL290929B2 (https=) |
| MX (1) | MX2022002686A (https=) |
| WO (1) | WO2021043870A1 (https=) |
| ZA (1) | ZA202203775B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024177394A1 (ko) * | 2023-02-24 | 2024-08-29 | 연세대학교 산학협력단 | 인덴 유도체를 유효성분으로 포함하는 섬유화의 예방 또는 치료용 조성물 |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的ペプチダーゼ30(usp30)阻害剤として有用な縮合二環化合物 |
| LT3860989T (lt) * | 2018-10-05 | 2023-06-12 | Forma Therapeutics, Inc. | Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai |
| WO2021204856A1 (en) | 2020-04-08 | 2021-10-14 | Mission Therapeutics Limited | N-cyanopyrrolidines with activity as usp30 inhibitors |
| IL298526A (en) | 2020-05-28 | 2023-01-01 | Mission Therapeutics Ltd | N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction |
| BR112022019722A2 (pt) | 2020-06-04 | 2022-12-20 | Mission Therapeutics Ltd | N-cianopirrolidinas com atividade como inibidores de usp30 |
| DK4161929T3 (da) | 2020-06-08 | 2025-08-18 | Mission Therapeutics Ltd | 1-(5-(2-cyanopyridin-4-yl)oxazol-2-carbonyl)-4-methylhexahydropyrrolo[3,4-b]pyrrol-5(1h)-carbonitril som usp30-hæmmer til anvendelse i behandling af mitokondriedysfunktion, cancer og fibrose |
| GB202016800D0 (en) | 2020-10-22 | 2020-12-09 | Mission Therapeutics Ltd | Novel compounds |
| US20250034122A1 (en) | 2021-12-01 | 2025-01-30 | Mission Therapeutics Limited | Substituted n-cyanopyrrolidines with activity as usp30 inhibitors |
| GB202408928D0 (en) | 2024-06-21 | 2024-08-07 | Mission Therapeutics Ltd | Novel compounds |
| GB202411060D0 (en) | 2024-07-29 | 2024-09-11 | Mission Therapeutics Ltd | Novel compounds |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9518953D0 (en) | 1995-09-15 | 1995-11-15 | Pfizer Ltd | Pharmaceutical formulations |
| WO2001077073A1 (en) | 2000-04-06 | 2001-10-18 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| WO2007119214A2 (en) | 2006-04-13 | 2007-10-25 | Actelion Pharmaceuticals Ltd | Endothelin receptor antagonists for early stage idiopathic pulmonary fibrosis |
| US8242271B2 (en) | 2007-06-04 | 2012-08-14 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| PE20090606A1 (es) | 2007-08-20 | 2009-06-17 | Glaxo Group Ltd | Nuevos inhibidores de catepsina c y uso |
| PE20091843A1 (es) | 2008-04-18 | 2010-01-07 | Glaxo Group Ltd | Inhibidores de catepsina c |
| TW201002318A (en) | 2008-04-18 | 2010-01-16 | Glaxo Group Ltd | Cathepsin C inhibitors |
| WO2009129370A1 (en) | 2008-04-18 | 2009-10-22 | Glaxo Group Limited | Cathepsin c inhibitors |
| US20120309820A1 (en) | 2011-06-04 | 2012-12-06 | Jb Therapeutics Inc. | Methods of treating fibrotic diseases using tetrahydrocannabinol-11-oic acids |
| EP2565186A1 (en) | 2011-09-02 | 2013-03-06 | Hybrigenics S.A. | Selective and reversible inhibitors of ubiquitin specific protease 7 |
| CA2918242C (en) | 2013-07-31 | 2022-06-21 | Merck Patent Gmbh | Pyridines, pyrimidines, and pyrazines, as btk inhibitors and uses thereof |
| US9963444B2 (en) | 2014-05-19 | 2018-05-08 | Northeastern University | N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof |
| WO2015183987A1 (en) | 2014-05-27 | 2015-12-03 | Pharmakea, Inc. | Compositions and methods of delivery of deubiquitinase inhibitors |
| WO2016019237A2 (en) | 2014-07-31 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| CA2960277A1 (en) * | 2014-09-10 | 2016-03-17 | Epizyme, Inc. | Substituted pyrrolidine carboxamide compounds |
| GB201416754D0 (en) * | 2014-09-23 | 2014-11-05 | Mission Therapeutics Ltd | Novel compounds |
| MX373656B (es) * | 2015-03-30 | 2020-04-02 | Mission Therapeutics Ltd | Compuestos de 1-ciano-pirrolidina como inhibidores de las enzimas desubiquitinantes, como la hidrolasa 30 de la c-terminal de la ubiquitina (usp30), y el uso de los mismos en el tratamiento de condiciones de disfunción mitocondrial y tratamiento de cancér. |
| US10669234B2 (en) | 2015-07-14 | 2020-06-02 | Mission Therapeutics Limited | Cyanopyrrolidines as dub inhibitors for the treatment of cancer |
| GB201521109D0 (en) | 2015-11-30 | 2016-01-13 | Mission Therapeutics Ltd | Novel compounds |
| GB201522267D0 (en) | 2015-12-17 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201522768D0 (en) | 2015-12-23 | 2016-02-03 | Mission Therapeutics Ltd | Novel compounds |
| GB201602854D0 (en) | 2016-02-18 | 2016-04-06 | Mission Therapeutics Ltd | Novel compounds |
| GB201603779D0 (en) | 2016-03-04 | 2016-04-20 | Mission Therapeutics Ltd | Novel compounds |
| GB201604647D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| GB201604638D0 (en) | 2016-03-18 | 2016-05-04 | Mission Therapeutics Ltd | Novel compounds |
| JP6959252B2 (ja) * | 2016-03-24 | 2021-11-02 | ミッション セラピューティクス リミティド | Dub阻害剤としての1−シアノピロリジン誘導体 |
| ES2850349T3 (es) | 2016-09-27 | 2021-08-27 | Mission Therapeutics Ltd | Derivados de cianopirrolidina con actividad como inhibidores de USP30 |
| GB201616511D0 (en) | 2016-09-29 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| GB201616627D0 (en) | 2016-09-30 | 2016-11-16 | Mission Therapeutics Limited | Novel compounds |
| TWI771327B (zh) | 2016-10-05 | 2022-07-21 | 英商使命醫療公司 | 新穎化合物 |
| US10968172B2 (en) | 2017-05-15 | 2021-04-06 | Mitobridge, Inc. | USP30 inhibitors |
| GB201708652D0 (en) | 2017-05-31 | 2017-07-12 | Mission Therapeutics Ltd | Novel compounds and uses |
| GB2563595B (en) | 2017-06-19 | 2020-04-15 | Edwards Ltd | Twin-shaft pumps |
| BR112020003725A2 (pt) | 2017-10-06 | 2020-11-03 | Forma Therapeutics, Inc. | inibição da peptidase 30 específica de ubiquitina |
| GB2571731A (en) | 2018-03-06 | 2019-09-11 | Mission Therapeutics Ltd | Novel compounds and uses |
| JP7449242B2 (ja) | 2018-05-17 | 2024-03-13 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的ペプチダーゼ30(usp30)阻害剤として有用な縮合二環化合物 |
| JP7434285B2 (ja) | 2018-08-14 | 2024-02-20 | アムジエン・インコーポレーテツド | N-シアノ-7-アザノルボルナン誘導体及びその使用 |
| LT3860989T (lt) | 2018-10-05 | 2023-06-12 | Forma Therapeutics, Inc. | Sulieti pirolinai, kurie veikia kaip ubikvitinui specifinės proteazės 30 (ups30) inhibitoriai |
| IL298526A (en) * | 2020-05-28 | 2023-01-01 | Mission Therapeutics Ltd | N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction |
-
2019
- 2019-09-04 GB GBGB1912674.7A patent/GB201912674D0/en not_active Ceased
-
2020
- 2020-09-03 WO PCT/EP2020/074540 patent/WO2021043870A1/en not_active Ceased
- 2020-09-03 BR BR112022003527A patent/BR112022003527A2/pt unknown
- 2020-09-03 JP JP2022514513A patent/JP2022546717A/ja not_active Ceased
- 2020-09-03 KR KR1020227010882A patent/KR20220054867A/ko not_active Withdrawn
- 2020-09-03 MX MX2022002686A patent/MX2022002686A/es unknown
- 2020-09-03 IL IL290929A patent/IL290929B2/en unknown
- 2020-09-03 CA CA3146040A patent/CA3146040A1/en active Pending
- 2020-09-03 AU AU2020340527A patent/AU2020340527A1/en active Pending
- 2020-09-03 EP EP20771779.4A patent/EP4025573B9/en active Active
- 2020-09-03 CN CN202080061743.3A patent/CN114341133B/zh active Active
- 2020-09-03 US US17/639,015 patent/US20220315572A1/en not_active Abandoned
-
2022
- 2022-03-25 CO CONC2022/0003608A patent/CO2022003608A2/es unknown
- 2022-04-01 ZA ZA2022/03775A patent/ZA202203775B/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024177394A1 (ko) * | 2023-02-24 | 2024-08-29 | 연세대학교 산학협력단 | 인덴 유도체를 유효성분으로 포함하는 섬유화의 예방 또는 치료용 조성물 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL290929A (en) | 2022-04-01 |
| EP4025573A1 (en) | 2022-07-13 |
| GB201912674D0 (en) | 2019-10-16 |
| JP2022546717A (ja) | 2022-11-07 |
| BR112022003527A2 (pt) | 2022-05-17 |
| CN114341133B (zh) | 2024-02-27 |
| ZA202203775B (en) | 2024-01-31 |
| EP4025573B9 (en) | 2024-11-20 |
| CO2022003608A2 (es) | 2022-04-19 |
| WO2021043870A1 (en) | 2021-03-11 |
| AU2020340527A1 (en) | 2022-04-21 |
| IL290929B1 (en) | 2024-11-01 |
| MX2022002686A (es) | 2022-04-07 |
| EP4025573B1 (en) | 2024-07-24 |
| US20220315572A1 (en) | 2022-10-06 |
| CA3146040A1 (en) | 2021-03-11 |
| CN114341133A (zh) | 2022-04-12 |
| IL290929B2 (en) | 2025-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114341133B (zh) | 具有usp30抑制剂活性的取代的氰基吡咯烷类 | |
| EP4157834B1 (en) | N-(1-cyano-pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)oxazole-2-carboxamide derivatives and the corresponding oxadiazole derivatives as usp30 inhibitors for the treatment of mitochondrial dysfunction | |
| KR20230006487A (ko) | Usp30 억제제로서의 활성을 갖는 n-시아노피롤리딘 | |
| WO2020212350A1 (en) | Substituted cyanopyrrolidines with activity as usp30 inhibitors | |
| JP7796047B2 (ja) | Usp30阻害剤としての活性を有するn-シアノピロリジン | |
| KR20230022215A (ko) | 미토콘드리아 기능장애, 암 및 섬유증의 치료에 사용하기 위한 USP30 억제제로서 1-(5-(2-시아노피리딘-4-일)옥사졸-2-카보닐)-4-메틸헥사하이드로피롤로[3,4-b]피롤-5(1H)-카보니트릴 | |
| WO2022084479A1 (en) | N-cyanopyrrolidines with activity as usp30 inhibitors | |
| RU2822680C1 (ru) | Замещенные цианопирролидины, обладающие активностью ингибиторов USP30 | |
| RU2848457C1 (ru) | N-Цианопирролидины с активностью ингибиторов USP30 | |
| RU2844289C1 (ru) | 1-(5-(2-Цианопиридин-4-ил)оксазол-2-карбонил)-4-метилгексагидропирроло[3,4-b]пиррол-5(1H)-карбонитрил в качестве ингибитора USP30 для применения в лечении митохондриальной дисфункции, рака и фиброза | |
| HK40068349A (en) | Substituted cyanopyrrolidines with activity as usp30 inhibitors | |
| HK40077361A (en) | N-cyanopyrrolidines with activity as usp30 inhibitors | |
| WO2026027857A1 (en) | N-cyanopyrrolidine deviratives having activity as inhibiotrs of ubiquitin specific peptidase 30 | |
| HK40068349B (zh) | 具有usp30抑制剂活性的取代的氰基吡咯烷类 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20220401 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1202 | Submission of document of withdrawal before decision of registration |
Comment text: [Withdrawal of Procedure relating to Patent, etc.] Withdrawal (Abandonment) Patent event code: PC12021R01D Patent event date: 20250311 |
|
| WITB | Written withdrawal of application |