JP2013532970A5 - - Google Patents

Info

Publication number

JP2013532970A5

JP2013532970A5 JP2013515850A JP2013515850A JP2013532970A5 JP 2013532970 A5 JP2013532970 A5 JP 2013532970A5 JP 2013515850 A JP2013515850 A JP 2013515850A JP 2013515850 A JP2013515850 A JP 2013515850A JP 2013532970 A5 JP2013532970 A5 JP 2013532970A5

Authority

JP

Japan

Prior art keywords

human insulin

cysteine

amino acid

chain

analogue according

Prior art date

2011-06-21

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.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims 79
• 101000976075 Homo sapiens Insulin Proteins 0.000 claims 45
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 27
• 235000018417 cysteine Nutrition 0.000 claims 22
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 20
• 102200127556 rs34159654 Human genes 0.000 claims 16
• 239000008194 pharmaceutical composition Substances 0.000 claims 13
• 235000001014 amino acid Nutrition 0.000 claims 11
• 125000000539 amino acid group Chemical group 0.000 claims 10
• 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 10
• 102220030552 rs398124174 Human genes 0.000 claims 8
• 238000006467 substitution reaction Methods 0.000 claims 8
• 125000003275 alpha amino acid group Chemical group 0.000 claims 7
• 230000015572 biosynthetic process Effects 0.000 claims 5
• 239000004026 insulin derivative Substances 0.000 claims 4
• 108090001061 Insulin Proteins 0.000 claims 3
• 102000004877 Insulin Human genes 0.000 claims 3
• 108091028043 Nucleic acid sequence Proteins 0.000 claims 3
• 150000001413 amino acids Chemical class 0.000 claims 3
• 230000004071 biological effect Effects 0.000 claims 3
• 229940125396 insulin Drugs 0.000 claims 3
• 238000000034 method Methods 0.000 claims 3
• 150000007523 nucleic acids Chemical group 0.000 claims 3
• 102000003746 Insulin Receptor Human genes 0.000 claims 2
• 108010001127 Insulin Receptor Proteins 0.000 claims 2
• 239000003937 drug carrier Substances 0.000 claims 2
• 239000013604 expression vector Substances 0.000 claims 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims 2
• 102000005962 receptors Human genes 0.000 claims 2
• 108020003175 receptors Proteins 0.000 claims 2
• 230000000717 retained effect Effects 0.000 claims 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
• 206010061818 Disease progression Diseases 0.000 claims 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
• 208000002705 Glucose Intolerance Diseases 0.000 claims 1
• 241000124008 Mammalia Species 0.000 claims 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
• 239000002671 adjuvant Substances 0.000 claims 1
• 239000008280 blood Substances 0.000 claims 1
• 210000004369 blood Anatomy 0.000 claims 1
• 238000012258 culturing Methods 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 claims 1
• 230000005750 disease progression Effects 0.000 claims 1
• 239000008103 glucose Substances 0.000 claims 1
• 201000001421 hyperglycemia Diseases 0.000 claims 1
• 230000002608 insulinlike Effects 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 238000007911 parenteral administration Methods 0.000 claims 1
• 239000002243 precursor Substances 0.000 claims 1
• 201000009104 prediabetes syndrome Diseases 0.000 claims 1
• 230000002265 prevention Effects 0.000 claims 1
• 230000017854 proteolysis Effects 0.000 claims 1
• 238000002741 site-directed mutagenesis Methods 0.000 claims 1
• 230000000087 stabilizing effect Effects 0.000 claims 1
• 239000000126 substance Substances 0.000 claims 1