CN115364224B - Use of GLUT1 inhibitors as mitochondrial autophagy inducers - Google Patents
Use of GLUT1 inhibitors as mitochondrial autophagy inducers Download PDFInfo
- Publication number
- CN115364224B CN115364224B CN202211022336.9A CN202211022336A CN115364224B CN 115364224 B CN115364224 B CN 115364224B CN 202211022336 A CN202211022336 A CN 202211022336A CN 115364224 B CN115364224 B CN 115364224B
- Authority
- CN
- China
- Prior art keywords
- mitochondrial autophagy
- mitochondrial
- bay
- glut1
- stf
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000002438 mitochondrial effect Effects 0.000 title claims abstract description 71
- 230000004900 autophagic degradation Effects 0.000 title claims abstract description 65
- 108091006296 SLC2A1 Proteins 0.000 title claims abstract description 42
- 239000003112 inhibitor Substances 0.000 title claims abstract description 37
- 102000058063 Glucose Transporter Type 1 Human genes 0.000 title claims abstract description 5
- 239000000411 inducer Substances 0.000 title abstract description 16
- BKLJDIJJOOQUFG-UHFFFAOYSA-N 4-N-[1-[(4-cyanophenyl)methyl]-5-methyl-3-(trifluoromethyl)pyrazol-4-yl]-7-fluoroquinoline-2,4-dicarboxamide Chemical compound C(#N)C1=CC=C(CN2N=C(C(=C2C)NC(=O)C2=CC(=NC3=CC(=CC=C23)F)C(=O)N)C(F)(F)F)C=C1 BKLJDIJJOOQUFG-UHFFFAOYSA-N 0.000 claims abstract description 34
- 230000001939 inductive effect Effects 0.000 claims description 19
- 230000006698 induction Effects 0.000 claims description 6
- UGTJLJZQQFGTJD-UHFFFAOYSA-N Carbonylcyanide-3-chlorophenylhydrazone Chemical compound ClC1=CC=CC(NN=C(C#N)C#N)=C1 UGTJLJZQQFGTJD-UHFFFAOYSA-N 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- NGQPRVWTFNBUHA-UHFFFAOYSA-N 4-[[(4-tert-butylphenyl)sulfonylamino]methyl]-n-pyridin-3-ylbenzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)NCC1=CC=C(C(=O)NC=2C=NC=CC=2)C=C1 NGQPRVWTFNBUHA-UHFFFAOYSA-N 0.000 abstract description 29
- 230000006378 damage Effects 0.000 abstract description 3
- 208000027418 Wounds and injury Diseases 0.000 abstract 1
- 208000014674 injury Diseases 0.000 abstract 1
- 102100023536 Solute carrier family 2, facilitated glucose transporter member 1 Human genes 0.000 description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 30
- 201000010099 disease Diseases 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 23
- 210000003470 mitochondria Anatomy 0.000 description 22
- 239000008194 pharmaceutical composition Substances 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 14
- 238000000034 method Methods 0.000 description 11
- 230000015556 catabolic process Effects 0.000 description 8
- 238000006731 degradation reaction Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 7
- 102000034342 Calnexin Human genes 0.000 description 6
- 108010056891 Calnexin Proteins 0.000 description 6
- 206010063837 Reperfusion injury Diseases 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 230000004770 neurodegeneration Effects 0.000 description 6
- 208000015122 neurodegenerative disease Diseases 0.000 description 6
- 206010061481 Renal injury Diseases 0.000 description 5
- 101150057558 Timm23 gene Proteins 0.000 description 5
- FRSWCCBXIHFKKY-UHFFFAOYSA-N [3-fluoro-2-(3-hydroxybenzoyl)oxyphenyl] 3-hydroxybenzoate Chemical compound OC1=CC=CC(C(=O)OC=2C(=C(F)C=CC=2)OC(=O)C=2C=C(O)C=CC=2)=C1 FRSWCCBXIHFKKY-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 208000019622 heart disease Diseases 0.000 description 5
- 208000037806 kidney injury Diseases 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- XKOYTLRGOQTKAU-UHFFFAOYSA-N 2-[3-[6-ethoxy-4-[4-(1H-pyrazol-4-yl)anilino]quinazolin-2-yl]phenoxy]-N-propan-2-ylacetamide Chemical compound N1N=CC(=C1)C1=CC=C(C=C1)NC1=NC(=NC2=CC=C(C=C12)OCC)C=1C=C(OCC(=O)NC(C)C)C=CC=1 XKOYTLRGOQTKAU-UHFFFAOYSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- 208000023105 Huntington disease Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WNTAQMQIZGJASL-UHFFFAOYSA-N 5-[[4-chloro-2-[(3-hydroxy-4-methylphenyl)methylamino]anilino]methyl]-2-methylphenol Chemical compound CC1=C(C=C(C=C1)CNC2=C(C=C(C=C2)Cl)NCC3=CC(=C(C=C3)C)O)O WNTAQMQIZGJASL-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 230000004642 autophagic pathway Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000006676 mitochondrial damage Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000042092 Glucose transporter family Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 210000004957 autophagosome Anatomy 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- -1 1H-pyrazolyl-4-yl Chemical group 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 235000008495 Chrysanthemum leucanthemum Nutrition 0.000 description 1
- 235000000604 Chrysanthemum parthenium Nutrition 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000002091 Febrile Seizures Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108091052347 Glucose transporter family Proteins 0.000 description 1
- 206010056328 Hepatic ischaemia Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000035177 MELAS Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 240000004460 Tanacetum coccineum Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000004922 autophagy dysfunction Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 206010016284 febrile convulsion Diseases 0.000 description 1
- 235000008384 feverfew Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004065 mitochondrial dysfunction Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- 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
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application discloses application of a GLUT1 inhibitor as a mitochondrial autophagy inducer. The application provides a novel application of GLUT1 inhibitor as a mitochondrial autophagy inducer, and in a preferred embodiment of the invention, BAY-876 and STF-31 can be used as the mitochondrial autophagy inducer to have outstanding selective induced injury mitochondrial autophagy.
Description
Technical Field
The invention relates to the field of chemical medicaments, in particular to application of a GLUT1 inhibitor as a mitochondrial autophagy inducer.
Background
Glucose transporter 1 (GLUT 1) inhibitors are commonly used to inhibit the expression level of glucose transporter 1 and thus the proliferation of cancer cells, such as the proliferation of lung cancer cells and breast cancer cells.
Mitochondria act as energy metabolism centers in cells, regulating cell death and inflammation. The cell controls the quality of mitochondria through mitochondrial autophagy, ensures the normal physiological process of the cell and reduces the inflammation level. Mitochondrial autophagy is an important physiological process in cells and is closely related to the occurrence and development of various diseases. Such as neurodegenerative diseases, inflammation, autoimmune diseases, infectious diseases, etc. The mechanism of these diseases is still unclear and there is no effective treatment in the prior art. The present inventors have found in the study that, in the progress of diseases related to mitochondrial autophagy, damage accumulation occurs due to mitochondrial dysfunction, which further aggravates mitochondrial autophagy dysfunction, so that cells cannot suppress inflammation or other symptoms by clearing damaged mitochondria, thereby suppressing disease progression. At this time, induction of mitochondrial autophagy can effectively help cells restart the mitochondrial quality control process, thereby clearing damaged mitochondria, relieving disease symptoms and hopefully curing such refractory diseases.
However, there is no successful development of a mitochondrial autophagy inducer suitable for clinical treatment. Thus, there is a need in the art to develop new mitochondrial autophagy inducers.
Disclosure of Invention
The invention aims to provide application of a GLUT1 inhibitor.
It is another object of the present invention to provide a method of inducing mitochondrial autophagy.
It is another object of the present invention to provide a method for preventing and/or treating diseases associated with mitochondrial autophagy.
To solve the above technical problem, the first aspect of the present invention provides the use of a GLUT1 inhibitor for the preparation of a medicament or pharmaceutical composition for one or more uses selected from the group consisting of:
(i) Inducing mitochondrial autophagy (as a mitochondrial autophagy inducer); and
(ii) Preventing and/or treating diseases related to mitochondrial autophagy.
In some preferred embodiments, the inducing mitochondrial autophagy is selectively inducing damaged mitochondrial autophagy, more preferably selectively inducing damaged mitochondrial autophagy caused by CCCP.
In some preferred embodiments, the GLUT1 inhibitor is BAY-876 or STF-31.
In some preferred embodiments, the selectively inducing damaged mitochondrial autophagy comprises:
selectively induces the degradation of damaged mitochondrial marking protein Tim23, but does not affect the degradation of endoplasmic reticulum marking protein Calnexin.
In some preferred embodiments, the selectively inducing damaged mitochondrial autophagy comprises:
the fluorescence of the keima protein localized in the injured mitochondria is selectively enhanced, but the fluorescence intensity of the keima protein in the intact mitochondria is not affected.
In some preferred embodiments, the disease associated with mitochondrial autophagy is selected from at least one of ischemia reperfusion injury, neurodegenerative disease, kidney injury associated disease, heart disease and sepsis.
In some preferred embodiments, the neurodegenerative disease is selected from at least one of Alzheimer's Disease (AD), huntington's Disease (HD), parkinson's Disease (PD), amyotrophic Lateral Sclerosis (ALS), hypoxic ischemic brain injury, MELAS-type Mitochondrial Encephalomyopathy (MELAS), and feverfew-related diseases.
In some preferred embodiments, the kidney injury-related disorder is selected from at least one of acute kidney injury, diabetic nephropathy, and chronic kidney failure.
In some preferred embodiments, the heart disease is selected from at least one of cardiomyopathy, diabetic cardiomyopathy, and cardiovascular disease.
In some preferred embodiments, the ischemia reperfusion injury is selected from at least one of renal ischemia reperfusion injury, hepatic ischemia reperfusion injury, and cardiac ischemia reperfusion injury or brain ischemia reperfusion injury.
In a second aspect of the invention, there is provided a pharmaceutical composition comprising BAY-876 and STF-31, and a pharmaceutically acceptable carrier or excipient.
In a third aspect of the present invention, there is provided a method of inducing autophagy in mitochondria, the method comprising the steps of:
administering to the subject a mitochondrial autophagy inducer which is a GLUT1 inhibitor or a pharmaceutical composition according to the second aspect of the invention.
In some preferred embodiments, the inducing mitochondrial autophagy is selectively inducing damaged mitochondrial autophagy.
In some preferred embodiments, the GLUT1 inhibitor is BAY-876 or STF-31.
In a fourth aspect of the present invention, there is provided a method for preventing and/or treating a disease associated with mitochondrial autophagy, the method comprising the steps of:
administering to the subject a therapeutically effective amount of a GLUT1 inhibitor or a pharmaceutical composition according to the second aspect of the invention.
Compared with the prior art, the invention has at least the following advantages:
(1) The invention provides a new application of GLUT1 inhibitor as a mitochondrial autophagy inducer, and in a preferred embodiment of the invention, BAY-876 and STF-31 can be used as the mitochondrial autophagy inducer to have outstanding capacity of selectively inducing damaged mitochondrial autophagy;
(2) The invention also provides methods of treating difficult conditions associated with mitochondrial autophagy, including neurodegenerative diseases, kidney injury related diseases, heart diseases, sepsis, and the like, using GLUT1 inhibitors, preferably BAY-876 and STF-31.
(3) The invention also provides pharmaceutical compositions containing BAY-876 and STF-31, useful for selectively inducing damaged mitochondrial autophagy.
It is understood that within the scope of the present invention, the above-described technical features of the present invention and technical features specifically described below (e.g., in the examples) may be combined with each other to constitute new or preferred technical solutions. And are limited to a space, and are not described in detail herein.
Drawings
One or more embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings.
FIG. 1 is a graph showing the results of Tim23 and Calnexin levels in cells containing damaged mitochondria and undamaged mitochondria under treatment with BAY-876 according to an embodiment of the present invention;
FIG. 2 is a statistical thermogram of fluorescence of cells containing damaged mitochondria and undamaged mitochondria in BAY-876 and STF-31 treatments, respectively, according to an embodiment of the present invention.
Detailed Description
Existing developments have demonstrated that mitochondrial autophagy is associated with the pathological course of a variety of problematic diseases. Glucose transporter 1 (GLUTs) is the major vector mediating glucose transport in mammalian cells, with the subtype GLUT1 being most widely distributed among glucose transporters in vivo. The existing research shows that the expression level of GLUT1 is related to various cancers to different degrees, so that the GLUT1 inhibitor is used for resisting cancers in the prior art. Through extensive and intensive studies, the present inventors have unexpectedly found that GLUT1 inhibitors (e.g., BAY-876 or STF-31) can be used as a mitochondrial autophagy inducer to induce mitochondrial autophagy or repair the mitochondrial autophagy pathway, and thus can be used for preventing and/or treating diseases associated with mitochondrial autophagy.
GLUT1 inhibitors
In the present invention, GLUT1 inhibitors refer to compounds, polypeptides and proteins that can inhibit the expression of glucose transporter 1. Commercial GLUT1 inhibitors are available commercially, and it will be appreciated by those skilled in the art that GLUT1 inhibitors as used herein are not limited to the compounds WZB117, DRB18, KL-11743, bay-876 and STF-31 disclosed herein.
In a preferred embodiment of the invention, the GLUT1 inhibitor is compound BAY-876 or STF-31.
In the invention, the structural formula of the compound BAY-876 is shown as formula I, wherein the name is as follows: n4- (1- (4-cyanobenzyl) -5-methyl-3- (trifluoromethyl) -1H-pyrazol-4-yl) -7-fluoroquinoline-2, 4-dicarboxamide, CAS number: 1799753-84-6.BAY-876 may be used as GLUT1 inhibitor.
In the invention, the structural formula of the compound STF-31 is shown as a formula II, wherein the name is as follows: 4- [ 4-tert-butylphenyl ] sulfonyl ] amino ] methyl ] -N-3-pyridylbenzamide having the CAS number: 724741-75-7.STF-31 may be used as a GLUT1 inhibitor.
In the invention, the structural formula of the compound WZB117 is shown in a formula III, wherein the name is as follows: 3-fluoro-1, 2-phenylenebis (3-hydroxybenzoate) with CAS number: 1223397-11-2.WZB117 may be used as GLUT1 inhibitor.
In the invention, the structural formula of the compound DRB18 is shown as a formula IV. DRB18 may be used as GLUT1 inhibitor.
In the invention, the structural formula of the compound KL-11743 is shown as a formula V, wherein the name is as follows: acetamide, 2- [3- [ 6-ethoxy-4- [4- (1H-pyrazolyl-4-yl) phenyl ] amino ] -2-quinazolinyl ] phenoxy ] -N- (1-methylethyl) -, CAS number: 1369452-53-8.KL-11743 can be used as GLUT1 inhibitors.
Mitochondrial autophagy inducer
In the present invention, a mitochondrial autophagy inducer refers to a compound that can selectively degrade damaged mitochondria (e.g., CCCP damaged mitochondria) in an autophagy pathway. The mitochondrial autophagy pathway comprises the processes of recognizing damaged mitochondria, activating mitochondrial autophagy receptors, wrapping the damaged mitochondria by autophagosomes, fusing the autophagosomes with lysosomes, degrading the mitochondria by the lysosomes and the like. Mitochondrial autophagy inducers may function in multiple processes.
Pharmaceutical composition
In the present invention, the pharmaceutical composition comprises an active ingredient, and a pharmaceutically acceptable carrier or excipient; wherein the active ingredient comprises BAY-876 and/or STF-31.
In a preferred embodiment of the invention, the active ingredients include BAY-876 and STF-31.
In the present invention, an "active ingredient" refers to a compound that is administered to a subject to treat, prevent or alleviate one or more symptoms of a condition, disorder or disease, alone or in combination with one or more pharmaceutically acceptable excipients. As used herein, an "active ingredient" and an "active agent" may be a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, isotopic variant, or tautomer of a compound described herein.
In the present invention, "pharmaceutically acceptable carriers and excipients" refer to pharmaceutically acceptable materials, compositions or vehicles, such as liquid or solid fillers, diluents, solvents or encapsulating materials. In one embodiment, each component is "pharmaceutically acceptable" in the sense that it is compatible with the other components of the pharmaceutical formulation and is suitable for contact with tissues or organs of humans and animals without undue toxicity, irritation, allergic response, immunogenicity, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
The pharmaceutical compositions of the present invention may be formulated with pharmaceutically acceptable carriers and/or vehicles as described above, ultimately providing several forms, both unit dosage forms and multi-dose forms. Non-limiting examples of formulations include, but are not limited to, oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, topical formulations such as ointments and creams, suppositories and sterile injectable solutions, preferably oral formulations or sterile injectable solutions.
Use of the same
The GLUT1 inhibitors of the present invention may be used in the preparation of a medicament or pharmaceutical composition for one or more uses selected from the group consisting of:
(i) Inducing mitochondrial autophagy;
(ii) Preventing and/or treating diseases related to mitochondrial autophagy.
In a preferred embodiment of the invention, the induction of mitochondrial autophagy is selective induction of damaged mitochondrial autophagy, more preferably selective induction of damaged mitochondrial autophagy caused by CCCP.
In the present invention, the term "inducing mitochondrial autophagy" refers to inducing targeted phagocytosis or destruction of mitochondria by cells.
In the present invention, the term "selectively induce damaged mitochondrial autophagy" refers to an autophagy manner that selectively isolates and degrades damaged or incomplete mitochondria without affecting or only minimally affecting intact mitochondria.
In a preferred embodiment of the invention, the GLUT1 inhibitor is BAY-876 or STF-31. Compared with other GLUT1 inhibitors, the two inhibitors have outstanding capability of selectively inducing damaged mitochondrial autophagy, namely, the damaged mitochondrial autophagy can be selectively induced.
In a preferred embodiment of the invention, BAY-876 or a pharmaceutical composition comprising the same, STF-31 or a pharmaceutical composition comprising the same, BAY-876 and STF-31, the pharmaceutical compositions comprising BAY-876 and STF-31 each having an outstanding ability to selectively induce damaged mitochondrial autophagy.
"Selectivity" can be verified by various means conventional in the art. In a preferred embodiment of the invention, selectively inducing damaged mitochondrial autophagy comprises: the fluorescence of the keima protein localized in the injured mitochondria is selectively enhanced, but the fluorescence intensity of the keima protein in the intact mitochondria is not affected. In a preferred further embodiment of the invention, selectively inducing damaged mitochondrial autophagy comprises: selectively induces the degradation of damaged mitochondrial marking protein Tim23, but does not affect the degradation of endoplasmic reticulum marking protein Calnexin.
Indication of disease
In the present invention, GLUT1 inhibitors are useful for preventing and/or treating diseases associated with mitochondrial autophagy. Such as neurodegenerative diseases, diseases associated with kidney injury, heart diseases, sepsis, etc.
Neurodegenerative diseases such as, but not limited to, alzheimer's Disease (AD), huntington's Disease (HD), parkinson's Disease (PD), amyotrophic Lateral Sclerosis (ALS), hypoxic ischemic brain injury, MELAS type Mitochondrial Encephalomyopathy (MELAS), and febrile convulsion-related diseases.
The kidney injury-related diseases are not limited, and include acute kidney injury, diabetic nephropathy, chronic renal failure, and the like.
Heart diseases such as, without limitation, cardiomyopathy, diabetic cardiomyopathy, cardiovascular disease, and the like.
Therapeutic method
In the present invention, a method for treating the above indications comprises the steps of: a therapeutically effective amount of a GLUT1 inhibitor, preferably BAY-876, STF-31, or a pharmaceutical composition of the invention, is administered to a subject.
In the present invention, the term "subject" is defined herein to include animals, such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, and the like. In a particular embodiment, the subject is a human.
In order to accommodate the characteristics of the subject and the need for treatment, the manner of administering the "GLUT1 inhibitor" or "pharmaceutical composition" to the subject is not limited in the present invention, and alternative administration modes include: enteral administration (oral, sublingual, rectal), parenteral injection (intravenous, subcutaneous, intramuscular, intraperitoneal), pulmonary absorption, or absorption via the conjunctiva, nasopharynx, oral, rectal, urinary tract, or bladder, in one embodiment, the subject is administered enterally.
As used herein, a "therapeutically effective amount" of a compound means an amount of the compound that is sufficient to provide a therapeutic effect in the treatment or management of a disease or disorder, or to delay or minimize one or more symptoms associated with the disease or disorder. A therapeutically effective amount of a compound refers to the amount of a therapeutic agent that, when used alone or in combination with other therapies, provides a therapeutic effect in the treatment or management of a disease or disorder. The term "therapeutically effective amount" may include an amount that improves overall therapy, reduces or avoids symptoms or causes of a disease or disorder, or enhances the therapeutic efficacy of another therapeutic agent.
In the present invention, a safe and effective amount of the "GLUT1 inhibitor" or the "pharmaceutical composition" is administered to a subject, wherein the safe and effective amount is 10 to 2000mg/kg, preferably 10 to 100 mg/kg; for example: 10mg/kg, 20mg/kg, 30mg/kg, 40mg/kg, 50mg/kg, 100mg/kg, the safe and effective amounts being the content of the active ingredients. In some embodiments, the safe and effective amount is 50-200mg/kg (mouse), or 500-1000mg/kg (human).
In the present invention, the "GLUT1 inhibitor" or "pharmaceutical composition" is administered 1 to 3 times daily, e.g., 1 time in the morning or evening, 2 times each in the morning or 3 times each in the morning, in the evening; the administration is continued for not less than 1 day, preferably not less than 3 days, preferably not less than 5 days, preferably not less than 7 days, most preferably not less than 7 days.
The present invention will be further described with reference to specific embodiments in order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent. It is to be understood that these examples are illustrative of the present invention and are not intended to limit the scope of the present invention. The experimental methods, in which specific conditions are not noted in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer. Percentages and parts are weight percentages and parts unless otherwise indicated. The experimental materials and reagents used in the following examples were obtained from commercial sources unless otherwise specified.
Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs, it is to be noted that the terms used herein are used merely to describe specific embodiments and are not intended to limit the exemplary embodiments of this application.
Example 1, immunohybridization experiments verify that HEK293T cells (ex ECACC) that specifically induce selective mitochondrial autophagy were seeded at a density of 2x 105/ml in 6-well plates at 2ml per well. 6 wells per cell. After 24 hours, BAY-876 or STF-31 was added at a final concentration of 5. Mu.M without adding and adding 3. Mu.M CCCP (carboyl cyanide 3-chlorophenylhydrozone, causing mitochondrial damage), respectively. After 12 hours, samples were collected in 250. Mu.l of 2XSDS loading buffer. Heated at 100℃for 10 minutes.
Immune hybridization: 10 μl of each sample was loaded and run for 90V2h; transfer film 300mA for 1h.5% skim milk was blocked for 1h at room temperature, antibody (Tim 23 antibody from Proteintech, #11123-1-AP; tubulin antibody from Hangzhou Hua Biotechnology Co., ltd., # M1305-2; calnexin antibody from Cell Signaling Technology, # 2433S) was incubated overnight at 4℃at a dilution ratio (Tubulin antibody 1:5000, the remainder 1:1000), and PBST (phosphate buffer+0.1% Tween 20) was washed 3 times for 10 minutes each time. Secondary antibodies (coat anti-Mouse IgG (h+l) secondary antibodies were purchased from Thermo Fisher Scientific, #31430; coat anti-Mouse IgG (h+l) secondary antibodies were purchased from Thermo Fisher Scientific, # 31460) at 1: the dilution ratio 20000 was incubated for 1h at room temperature and the pbst washes were performed 3 times for 10 minutes each. ECL color development.
As shown in FIG. 1, the immunohybridization (western blot) test shows that BAY-876 and STF-31 do not cause degradation of mitochondrial marker protein Tim23 in HEK293T cells and do not affect degradation of endoplasmic reticulum marker protein Calnexin. In the case of mitochondrial damage caused by the addition of CCCP, BAY-876 and STF-31 resulted in degradation of the mitochondrial marking protein Tim23, but also did not affect degradation of the endoplasmic reticulum marking protein Calnexin. This suggests that BAY-876 and STF-31 specifically induce the occurrence of selective mitochondrial autophagy without affecting the occurrence of other autophagies.
Example 2, keima fluorescence assay to verify that BAY-876 induces selective mitochondrial autophagy
Human embryonic kidney transformed cells HEK293Tmtkeima cells (cell lines which indicate the onset of mitochondrial autophagy, stable expression of mtkeima are self-constructs1.5.105 times/ml of biological preservation information CCTCC NO: C201940 2019.03.07) is planted in a 96-hole black ELISA plate, BAY-876 or STF-31 with the final concentration of 5 mu M is added, and 3 repeats are arranged; incubated at 37℃with 5% CO 2. Under the same conditions, the other group of cells is cultured in a 96-well black ELISA plate at a rate of 1.5 x 105 cells/ml, and 100 μl per well of HEK293Tmtkeima cells; after 24 hours, 3. Mu.M CCCP was added to induce mitochondrial breakage, and after 1 hour, BAY-876 or STF-31 was added at a final concentration of 5. Mu.M, and 3 replicates were set; at 37 ℃,5% CO 2 Culture conditions were photographed 12 hours later with biotek cell 5. The two groups take bright field as focusing channel, 4 pictures are taken from each hole, and the images are processed by using instrument software.
As shown in FIG. 2, the HEK293Tmtkeima system of human embryonic kidney transformed cells was treated with 3uM CCCP and then with BAY-876 or STF-31, which significantly increased keima signal compared to BAY-876 or STF-31 alone. And no significant increase in keima signal was seen after BAY-876 alone. It was demonstrated that BAY-876 did not cause mitochondrial damage and selectively induced mitochondrial autophagy in damaged mitochondria.
It will be understood by those of ordinary skill in the art that the foregoing embodiments are specific examples of carrying out the invention and that various changes in form and details may be made therein without departing from the spirit and scope of the invention.
Claims (1)
- Use of a glut1 inhibitor, for non-therapeutically inducing mitochondrial autophagy in vitro; the GLUT1 inhibitor is BAY-876;the induction of mitochondrial autophagy is selective induction of damaged mitochondrial autophagy caused by CCCP.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211022336.9A CN115364224B (en) | 2022-08-25 | 2022-08-25 | Use of GLUT1 inhibitors as mitochondrial autophagy inducers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211022336.9A CN115364224B (en) | 2022-08-25 | 2022-08-25 | Use of GLUT1 inhibitors as mitochondrial autophagy inducers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115364224A CN115364224A (en) | 2022-11-22 |
| CN115364224B true CN115364224B (en) | 2024-02-02 |
Family
ID=84068141
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211022336.9A Active CN115364224B (en) | 2022-08-25 | 2022-08-25 | Use of GLUT1 inhibitors as mitochondrial autophagy inducers |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115364224B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017180063A1 (en) * | 2016-04-13 | 2017-10-19 | National University Of Singapore | A potential combination therapy using an inhibitor of glucose transport and an intracellular calcium inducer to target cancer metabolism |
| CN108697729A (en) * | 2016-02-04 | 2018-10-23 | 约翰霍普金斯大学 | Novel GLUT inhibitor rapaglutin and application thereof |
| WO2021007499A1 (en) * | 2019-07-11 | 2021-01-14 | Emory University | Combination therapies for managing cancer |
| CN112294815A (en) * | 2020-09-22 | 2021-02-02 | 厦门市中医院 | Application of compound BAY-876 in preparation of medicine for treating and/or preventing liver injury |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018201006A1 (en) * | 2017-04-28 | 2018-11-01 | Kadmon Corporation, Llc | Treatment of inflammatory conditions and autoimmune diseases with glucose uptake inhibitors |
-
2022
- 2022-08-25 CN CN202211022336.9A patent/CN115364224B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108697729A (en) * | 2016-02-04 | 2018-10-23 | 约翰霍普金斯大学 | Novel GLUT inhibitor rapaglutin and application thereof |
| WO2017180063A1 (en) * | 2016-04-13 | 2017-10-19 | National University Of Singapore | A potential combination therapy using an inhibitor of glucose transport and an intracellular calcium inducer to target cancer metabolism |
| WO2021007499A1 (en) * | 2019-07-11 | 2021-01-14 | Emory University | Combination therapies for managing cancer |
| CN112294815A (en) * | 2020-09-22 | 2021-02-02 | 厦门市中医院 | Application of compound BAY-876 in preparation of medicine for treating and/or preventing liver injury |
Non-Patent Citations (2)
| Title |
|---|
| GLUT1 特异性抑制剂 BAY-876 逆 转缺氧对 PASMC 的促增殖作用及 机制研究;宋楠楠;中国优秀硕士学位论文全文数据库 (医药卫生科技辑)(第2022年第05期期);E066-19 * |
| 糖尿病大鼠脑缺血再灌注后GLUT1和GLUT3蛋白表达变化;张雯雯;中国优秀硕士学位论文全文数据库 (医药卫生科技辑)(第2010年第05期期);E065-38 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115364224A (en) | 2022-11-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11602530B2 (en) | CRM1 inhibitors for treating epilepsy | |
| Wang et al. | Poloxamer-188 can attenuate blood–brain barrier damage to exert neuroprotective effect in mice intracerebral hemorrhage model | |
| EP3496751A1 (en) | Pharmaceutical combinations of histone deacetylase 6 inhibitors and cd20 inhibitory antibodies and uses thereof | |
| US20060058365A1 (en) | Compositions and methods for treatment of colitis | |
| JP7025358B2 (en) | How to Treat Immunoglobulin Light Chain Amyloidosis | |
| US11628146B2 (en) | Estrogen receptor ligand treatment for neurodegenerative diseases | |
| TW202003503A (en) | Method of treating fibrotic disease | |
| JP2016527312A (en) | Method for treating pruritic conditions mediated through histamine H4 receptors | |
| JP2022116304A (en) | PPAR-γ AGONIST FOR TREATMENT OF BLOOD CANCERS | |
| WO2024041596A1 (en) | Use of phenytoin sodium as mitophagy inducer | |
| CN115364224B (en) | Use of GLUT1 inhibitors as mitochondrial autophagy inducers | |
| US20150290168A1 (en) | Class iia hdac inhibitors for the treatment of infection | |
| TW202146016A (en) | Method for administration of an anti cancer agent | |
| CN114007607A (en) | Materials and methods for treating neurodegenerative diseases | |
| Tanaka et al. | Therapeutic effects of eperisone on pulmonary fibrosis via preferential suppression of fibroblast activity | |
| US20050070565A1 (en) | Chelerythrine, analogs thereof and their use in the treatment of bipolar disorder and other cognitive disorders | |
| TWI770608B (en) | Pharmaceutical compositions and uses thereof in treating parkinson's disease | |
| KR20200136428A (en) | Composition and method for treating severe constipation | |
| US10507228B2 (en) | Methods and compositions related to KRAS inhibitors | |
| US20070248702A1 (en) | Use of CB2 receptors agonists for the treatment of Huntington's disease | |
| US20230190845A1 (en) | Pharmaceutical compositions and uses thereof in treating parkinson's disease | |
| Mortazavi et al. | Prevalence and Risk Factors of Diabetes Mellitus in β-thalassemia Major Patients in the North of Iran: Mazandaran β-thalassemia Registry-2017 to 2019 | |
| WO2022007578A1 (en) | Combination for treating alzheimer's disease and use thereof | |
| JP2008255008A (en) | Synoviocyte proliferation inhibitor | |
| CN115364100B (en) | Use of LY2835219 as a mitochondrial autophagy inducer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |