AU6026698A - Modulators of insulin receptor activity - Google Patents
Modulators of insulin receptor activityInfo
- Publication number
- AU6026698A AU6026698A AU60266/98A AU6026698A AU6026698A AU 6026698 A AU6026698 A AU 6026698A AU 60266/98 A AU60266/98 A AU 60266/98A AU 6026698 A AU6026698 A AU 6026698A AU 6026698 A AU6026698 A AU 6026698A
- Authority
- AU
- Australia
- Prior art keywords
- insulin
- insulin receptor
- receptor
- chain
- independently
- 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.)
- Abandoned
Links
- 102000003746 Insulin Receptor Human genes 0.000 title claims abstract description 129
- 108010001127 Insulin Receptor Proteins 0.000 title claims abstract description 129
- 230000000694 effects Effects 0.000 title claims abstract description 128
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract description 219
- 150000001875 compounds Chemical class 0.000 claims abstract description 156
- 102000004877 Insulin Human genes 0.000 claims abstract description 109
- 108090001061 Insulin Proteins 0.000 claims abstract description 109
- 229940125396 insulin Drugs 0.000 claims abstract description 109
- 230000027455 binding Effects 0.000 claims abstract description 64
- 238000000034 method Methods 0.000 claims abstract description 64
- 230000004913 activation Effects 0.000 claims abstract description 61
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 50
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 50
- 239000000126 substance Substances 0.000 claims abstract description 48
- 230000026731 phosphorylation Effects 0.000 claims abstract description 35
- 238000006366 phosphorylation reaction Methods 0.000 claims abstract description 35
- 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 claims abstract description 33
- 239000008103 glucose Substances 0.000 claims abstract description 33
- 125000005647 linker group Chemical group 0.000 claims abstract description 30
- 125000003118 aryl group Chemical group 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 24
- 239000008280 blood Substances 0.000 claims abstract description 18
- 210000004369 blood Anatomy 0.000 claims abstract description 18
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 17
- 230000000638 stimulation Effects 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims abstract description 16
- 230000001086 cytosolic effect Effects 0.000 claims abstract description 11
- 230000008727 cellular glucose uptake Effects 0.000 claims abstract description 9
- 102000058061 Glucose Transporter Type 4 Human genes 0.000 claims abstract description 7
- 108091006300 SLC2A4 Proteins 0.000 claims abstract description 7
- 230000005945 translocation Effects 0.000 claims abstract description 7
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 claims abstract description 5
- 101710201824 Insulin receptor substrate 1 Proteins 0.000 claims abstract description 5
- 239000012190 activator Substances 0.000 claims description 26
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 239000000758 substrate Substances 0.000 claims description 13
- 238000012360 testing method Methods 0.000 claims description 11
- 230000003389 potentiating effect Effects 0.000 claims description 10
- 108091006112 ATPases Proteins 0.000 claims description 9
- 102000057290 Adenosine Triphosphatases Human genes 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 238000013461 design Methods 0.000 claims description 6
- 229910006127 SO3X Inorganic materials 0.000 claims description 5
- 230000004075 alteration Effects 0.000 claims description 5
- 239000012634 fragment Substances 0.000 claims description 5
- 238000012546 transfer Methods 0.000 claims description 4
- 230000035772 mutation Effects 0.000 claims description 3
- 101100205088 Caenorhabditis elegans iars-1 gene Proteins 0.000 claims description 2
- 101150030450 IRS1 gene Proteins 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 230000004190 glucose uptake Effects 0.000 abstract description 13
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 abstract description 3
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 abstract description 3
- 230000001151 other effect Effects 0.000 abstract 1
- 102000005962 receptors Human genes 0.000 description 100
- 108020003175 receptors Proteins 0.000 description 100
- 210000004027 cell Anatomy 0.000 description 44
- 108090000765 processed proteins & peptides Proteins 0.000 description 44
- 238000003556 assay Methods 0.000 description 31
- 102000004196 processed proteins & peptides Human genes 0.000 description 30
- 239000000523 sample Substances 0.000 description 25
- 230000008859 change Effects 0.000 description 21
- 235000002374 tyrosine Nutrition 0.000 description 18
- 230000035578 autophosphorylation Effects 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 12
- 102000047882 human INSR Human genes 0.000 description 12
- 150000003668 tyrosines Chemical class 0.000 description 12
- 230000003197 catalytic effect Effects 0.000 description 10
- 230000003993 interaction Effects 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 230000003213 activating effect Effects 0.000 description 9
- 238000000021 kinase assay Methods 0.000 description 8
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 8
- 210000001789 adipocyte Anatomy 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 125000000129 anionic group Chemical group 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 5
- -1 bromonium ion Chemical group 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000000539 dimer Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000009257 reactivity Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- KXGFMDJXCMQABM-UHFFFAOYSA-N 2-methoxy-6-methylphenol Chemical compound [CH]OC1=CC=CC([CH])=C1O KXGFMDJXCMQABM-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 208000020832 chronic kidney disease Diseases 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 230000006377 glucose transport Effects 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000813 peptide hormone Substances 0.000 description 3
- 239000005011 phenolic resin Substances 0.000 description 3
- 229920001568 phenolic resin Polymers 0.000 description 3
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 125000003831 tetrazolyl group Chemical group 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 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 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 2
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 101150110386 SLC2A4 gene Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001767 cationic compounds Chemical class 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910001411 inorganic cation Inorganic materials 0.000 description 2
- 230000004155 insulin signaling pathway Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 239000011565 manganese chloride Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 150000002892 organic cations Chemical class 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- 230000003169 placental effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- YAYQBMCWKKCSDG-UHFFFAOYSA-N 2-(3,5-dimethylanilino)-2-oxoacetic acid Chemical compound CC1=CC(C)=CC(NC(=O)C(O)=O)=C1 YAYQBMCWKKCSDG-UHFFFAOYSA-N 0.000 description 1
- FEHLIYXNTWAEBQ-UHFFFAOYSA-N 4-(4-formylphenyl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=C(C=O)C=C1 FEHLIYXNTWAEBQ-UHFFFAOYSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- HPGXYQZKIMWRAM-UHFFFAOYSA-N 4-ethylmorpholin-4-ium;acetate Chemical compound CC(O)=O.CCN1CCOCC1 HPGXYQZKIMWRAM-UHFFFAOYSA-N 0.000 description 1
- 239000004254 Ammonium phosphate Substances 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
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 101100456896 Drosophila melanogaster metl gene Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 101000837299 Euglena gracilis Trans-2-enoyl-CoA reductase Proteins 0.000 description 1
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 1
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 229940079288 Insulin receptor agonist Drugs 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 1
- 108010007843 NADH oxidase Proteins 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 108010025497 Raytide Proteins 0.000 description 1
- 241000589499 Thermus thermophilus Species 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 108010066657 azoreductase Proteins 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 230000034149 carbohydrate storage Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000013118 diabetic mouse model Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 125000000950 dibromo group Chemical group Br* 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005421 electrostatic potential Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000012203 high throughput assay Methods 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 102000055647 human CSF2RB Human genes 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 108010042209 insulin receptor tyrosine kinase Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 125000004957 naphthylene group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 230000002186 photoactivation Effects 0.000 description 1
- 239000007856 photoaffinity label Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 210000000229 preadipocyte Anatomy 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000005477 standard model Effects 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/33—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of six-membered aromatic rings being part of condensed ring systems
- C07C309/34—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of six-membered aromatic rings being part of condensed ring systems formed by two rings
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/575—Hormones
- G01N2333/62—Insulins
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
- G01N2333/9121—Phosphotransferases in general with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU34362/02A AU780473B2 (en) | 1997-01-15 | 2002-04-16 | Modulators of insulin receptor activity |
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78485597A | 1997-01-15 | 1997-01-15 | |
| US08784854 | 1997-01-15 | ||
| US08/784,857 US5830918A (en) | 1997-01-15 | 1997-01-15 | Nonpeptide insulin receptor agonists |
| US08/784,854 US5851988A (en) | 1997-01-15 | 1997-01-15 | Nonpeptide insulin receptor agonists |
| US08784855 | 1997-01-15 | ||
| US08784857 | 1997-01-15 | ||
| US82526997A | 1997-03-27 | 1997-03-27 | |
| US08825269 | 1997-03-27 | ||
| US08916088 | 1997-08-21 | ||
| US08/916,088 US6329431B1 (en) | 1997-01-15 | 1997-08-21 | Nonpeptide insulin receptor agonists |
| PCT/US1998/000801 WO1998032017A2 (en) | 1997-01-15 | 1998-01-15 | Modulators of insulin receptor activity |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU34362/02A Division AU780473B2 (en) | 1997-01-15 | 2002-04-16 | Modulators of insulin receptor activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU6026698A true AU6026698A (en) | 1998-08-07 |
Family
ID=27542207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU60266/98A Abandoned AU6026698A (en) | 1997-01-15 | 1998-01-15 | Modulators of insulin receptor activity |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0960335B1 (enExample) |
| JP (1) | JP2002512685A (enExample) |
| AT (1) | ATE296446T1 (enExample) |
| AU (1) | AU6026698A (enExample) |
| CA (1) | CA2278023A1 (enExample) |
| DE (1) | DE69830301T2 (enExample) |
| DK (1) | DK0960335T3 (enExample) |
| ES (1) | ES2242995T3 (enExample) |
| WO (1) | WO1998032017A2 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6875741B2 (en) * | 1998-09-02 | 2005-04-05 | Renuka Pillutla | Insulin and IGF-1 receptor agonists and antagonists |
| EP1115847A1 (en) | 1998-09-25 | 2001-07-18 | Children's Medical Center Corporation | Short peptides which selectively modulate the activity of protein kinases |
| TWI234557B (en) * | 1999-05-26 | 2005-06-21 | Telik Inc | Novel naphthalene ureas as glucose uptake enhancers |
| US7181349B1 (en) * | 1999-05-27 | 2007-02-20 | Cecil Yip | Identification of compounds for modulating dimeric receptors |
| ITTO20000745A1 (it) * | 1999-07-29 | 2002-01-28 | Telik Inc | Nuovi acidi naftilsolfonici e composti ad essi correlati utli come agonisti dell'assorbimento del glucosio. |
| FR2797767B1 (fr) * | 1999-08-27 | 2002-06-14 | Centre Nat Rech Scient | Utilisation d'acides amines pour la fabrication de medicaments destines au traitement des insulino-resistances |
| EP1383793B1 (en) * | 2000-03-29 | 2011-10-19 | DGI BioTechnologies, L.L.C. | Insulin and igf-1 receptor agonists and antagonists |
| WO2002055664A2 (en) * | 2001-01-12 | 2002-07-18 | Exelixis, Inc. | Modulating insulin receptor signaling |
| CN101103977A (zh) * | 2002-06-05 | 2008-01-16 | 株式会社医药分子设计研究所 | 糖尿病治疗药 |
| TW200410671A (en) * | 2002-06-05 | 2004-07-01 | Inst Med Molecular Design Inc | Medicines for inhibiting the activation of AP-1 |
| CN1658855B (zh) | 2002-06-06 | 2010-04-28 | 株式会社医药分子设计研究所 | O-取代羟基芳基衍生物 |
| CN1658872B (zh) * | 2002-06-06 | 2010-09-22 | 株式会社医药分子设计研究所 | 抗过敏药 |
| EP1535610A4 (en) * | 2002-06-10 | 2008-12-31 | Inst Med Molecular Design Inc | THERAPEUTIC CANCER |
| EA010470B1 (ru) * | 2002-06-10 | 2008-08-29 | Инститьют Оф Медисинал Молекьюлар Дизайн. Инк. | ИНГИБИТОРЫ АКТИВАЦИИ NF-kB |
| DE10323081A1 (de) * | 2003-05-22 | 2004-12-16 | Aventis Pharma Deutschland Gmbh | Verwendung eines Polypeptides |
| JP2008542685A (ja) * | 2005-05-05 | 2008-11-27 | ヴァロリザーシヨン・アッシュエスジ,ソシエテ・アン・コマンディット | サイトカイン受容体修飾因子及びその使用 |
| US7671058B2 (en) | 2006-06-21 | 2010-03-02 | Institute Of Medicinal Molecular Design, Inc. | N-(3,4-disubstituted phenyl) salicylamide derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995023231A1 (en) * | 1994-02-28 | 1995-08-31 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Cell lines for the identification of substances affecting insulin receptor mediated signal transduction |
| WO1996030762A1 (en) * | 1995-03-31 | 1996-10-03 | Merck & Co., Inc. | Insulin mimetic and enhancer assay |
-
1998
- 1998-01-15 EP EP98903515A patent/EP0960335B1/en not_active Expired - Lifetime
- 1998-01-15 DK DK98903515T patent/DK0960335T3/da active
- 1998-01-15 AU AU60266/98A patent/AU6026698A/en not_active Abandoned
- 1998-01-15 CA CA002278023A patent/CA2278023A1/en not_active Abandoned
- 1998-01-15 DE DE69830301T patent/DE69830301T2/de not_active Expired - Fee Related
- 1998-01-15 WO PCT/US1998/000801 patent/WO1998032017A2/en not_active Ceased
- 1998-01-15 JP JP53453298A patent/JP2002512685A/ja not_active Ceased
- 1998-01-15 AT AT98903515T patent/ATE296446T1/de not_active IP Right Cessation
- 1998-01-15 ES ES98903515T patent/ES2242995T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE69830301D1 (de) | 2005-06-30 |
| EP0960335B1 (en) | 2005-05-25 |
| EP0960335A2 (en) | 1999-12-01 |
| WO1998032017A2 (en) | 1998-07-23 |
| ES2242995T3 (es) | 2005-11-16 |
| CA2278023A1 (en) | 1998-07-23 |
| DK0960335T3 (da) | 2005-06-20 |
| DE69830301T2 (de) | 2006-02-02 |
| ATE296446T1 (de) | 2005-06-15 |
| JP2002512685A (ja) | 2002-04-23 |
| WO1998032017A3 (en) | 1999-02-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0960335B1 (en) | Modulators of insulin receptor activity | |
| US5830918A (en) | Nonpeptide insulin receptor agonists | |
| Walsh | Calmodulin and the regulation of smooth muscle contraction | |
| Tang et al. | Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis | |
| Margolis et al. | Activation of Ras by receptor tyrosine kinases. | |
| AU679253B2 (en) | Identification of ligands by selective amplification of cells transfected with receptors | |
| US5378809A (en) | Polynucleotides and substrate for the epidermal growth factor receptor kinase (eps8) | |
| US5851988A (en) | Nonpeptide insulin receptor agonists | |
| JP2000512737A (ja) | 試験管内蛍光偏光検定法 | |
| AU758115B2 (en) | Enzymatic fluorimetric assay of cAMP and adenylate cyclase | |
| WO1996040276A1 (en) | Screening assays for compounds | |
| US6329431B1 (en) | Nonpeptide insulin receptor agonists | |
| AU780473B2 (en) | Modulators of insulin receptor activity | |
| US20030078188A1 (en) | Modulators of insulin receptor activity | |
| Van Eldik et al. | Calmodulin structure and function | |
| US20110111980A1 (en) | Method for profiling drug compounds | |
| EP2157092A1 (en) | Remedy for diabetes | |
| Zhang et al. | An affinity-based fluorescence polarization assay for protein tyrosine phosphatases | |
| JP4437003B2 (ja) | Evh1ドメインまたはevh1ドメインを有するタンパク質とevh1結合ドメインまたはevh1結合ドメインを有するタンパク質との相互作用を調節する化合物をスクリーニングする方法およびその相互作用を検出する方法 | |
| US7070938B2 (en) | Method to detect modulators of VEGF kinase domain | |
| Formisano et al. | Antiphosphotyrosine immunoprecipitation of an insulin-stimulated receptor phosphatase activity from FRTL5 cells | |
| WO2003068927A2 (en) | Method for influencing kinase activity with ag879 and ag879 derivatives | |
| Müller | Assays for Insulin and Insulin-Like Signal Transduction Based on Adipocytes, Hepatocytes, and Myocytes | |
| Vera et al. | Svicevic, Marina, Mijailovich, Srbolujub M, Combs, Ariana C., Langer, Stephen J., Ruppel, Kathleen M., Spudich, James A and others (2019) Myosin Motor Domains Carrying Mutations Implicated in Early or Late Onset Hypertrophic Cardiomyopathy Have Similar Properties. Journal of Biological Chemistry | |
| KR20050112694A (ko) | 핵자기 공명 분광기를 이용한 인간 prl-3 단백질 활성조절제 선별 방법, 선별 장치 및 이를 위한 인간 prl-3단백질 절편 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |