ES2451349T3 - Inhibidores de CXCR1/2 como adyuvantes en el trasplante de islotes pancreáticos - Google Patents
Inhibidores de CXCR1/2 como adyuvantes en el trasplante de islotes pancreáticosInfo
- Publication number
- ES2451349T3 ES2451349T3 ES10761018.0T ES10761018T ES2451349T3 ES 2451349 T3 ES2451349 T3 ES 2451349T3 ES 10761018 T ES10761018 T ES 10761018T ES 2451349 T3 ES2451349 T3 ES 2451349T3
- Authority
- ES
- Spain
- Prior art keywords
- transplantation
- reparixin
- mice
- inhibitor
- cxcr1
- 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
- 238000002054 transplantation Methods 0.000 title claims abstract description 65
- 210000004153 islets of langerhan Anatomy 0.000 title claims abstract description 25
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 title claims abstract description 18
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 title claims abstract description 18
- 239000003112 inhibitor Substances 0.000 title claims abstract description 18
- 239000002671 adjuvant Substances 0.000 title description 4
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 claims abstract description 21
- 108010018951 Interleukin-8B Receptors Proteins 0.000 claims abstract description 21
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 8
- 229940127085 adjuvant medication Drugs 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 23
- 230000004083 survival effect Effects 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 206010052779 Transplant rejections Diseases 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 230000007774 longterm Effects 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
- 230000009919 sequestration Effects 0.000 claims 1
- KQDRVXQXKZXMHP-LLVKDONJSA-N reparixin Chemical compound CC(C)CC1=CC=C([C@@H](C)C(=O)NS(C)(=O)=O)C=C1 KQDRVXQXKZXMHP-LLVKDONJSA-N 0.000 description 55
- 229950005650 reparixin Drugs 0.000 description 53
- 241000699670 Mus sp. Species 0.000 description 51
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 40
- 239000008103 glucose Substances 0.000 description 40
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 23
- 229960002930 sirolimus Drugs 0.000 description 23
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 23
- 210000004369 blood Anatomy 0.000 description 21
- 239000008280 blood Substances 0.000 description 21
- 210000004185 liver Anatomy 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 13
- 206010012601 diabetes mellitus Diseases 0.000 description 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 description 10
- 230000000291 postprandial effect Effects 0.000 description 9
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 8
- 108010082126 Alanine transaminase Proteins 0.000 description 8
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 8
- 102100022338 Integrin alpha-M Human genes 0.000 description 8
- 230000000735 allogeneic effect Effects 0.000 description 7
- 210000000265 leukocyte Anatomy 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- 102100026236 Interleukin-8 Human genes 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 102100022297 Integrin alpha-X Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000001506 immunosuppresive effect Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 210000000581 natural killer T-cell Anatomy 0.000 description 4
- 238000007410 oral glucose tolerance test Methods 0.000 description 4
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000002650 immunosuppressive therapy Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 210000005228 liver tissue Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 238000000491 multivariate analysis Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 238000000611 regression analysis Methods 0.000 description 3
- 229960001967 tacrolimus Drugs 0.000 description 3
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 3
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000011316 allogeneic transplantation Methods 0.000 description 2
- 108010004469 allophycocyanin Proteins 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 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 2
- 238000007446 glucose tolerance test Methods 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 210000003622 mature neutrocyte Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- NAPRBFMJOYOQOA-UHFFFAOYSA-N 4-[4-(2-methylpropyl)phenyl]-2-oxobutane-1-sulfonamide Chemical compound C(C(C)C)C1=CC=C(C=C1)CCC(=O)CS(=O)(=O)N NAPRBFMJOYOQOA-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- 229940122444 Chemokine receptor antagonist Drugs 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 208000021709 Delayed Graft Function Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 206010001053 acute respiratory failure Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000002559 chemokine receptor antagonist Substances 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000005161 hepatic lobe Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000004923 pancreatic tissue Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09172364 | 2009-10-06 | ||
| EP09172364A EP2308484A1 (en) | 2009-10-06 | 2009-10-06 | Inhibitors of cxcr1/2 as adjuvants in the transplant of pancreatic islets |
| PCT/EP2010/064921 WO2011042466A1 (en) | 2009-10-06 | 2010-10-06 | Inhibitors of cxcr1/2 as adjuvants in the transplant of pancreatic islets |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2451349T3 true ES2451349T3 (es) | 2014-03-26 |
Family
ID=41818891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10761018.0T Active ES2451349T3 (es) | 2009-10-06 | 2010-10-06 | Inhibidores de CXCR1/2 como adyuvantes en el trasplante de islotes pancreáticos |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US20120202884A1 (https=) |
| EP (2) | EP2308484A1 (https=) |
| JP (2) | JP5834010B2 (https=) |
| KR (2) | KR101759362B1 (https=) |
| CN (2) | CN104906572A (https=) |
| AU (1) | AU2010305385B2 (https=) |
| BR (1) | BR112012007991B8 (https=) |
| CA (1) | CA2775902C (https=) |
| CY (1) | CY1115018T1 (https=) |
| DK (1) | DK2485723T3 (https=) |
| EA (1) | EA021298B1 (https=) |
| ES (1) | ES2451349T3 (https=) |
| HK (1) | HK1213777A1 (https=) |
| HR (1) | HRP20140202T1 (https=) |
| IL (1) | IL219037A (https=) |
| ME (1) | ME01719B (https=) |
| MX (1) | MX2012004082A (https=) |
| NZ (1) | NZ599172A (https=) |
| PL (1) | PL2485723T3 (https=) |
| PT (1) | PT2485723E (https=) |
| RS (1) | RS53249B (https=) |
| SI (1) | SI2485723T1 (https=) |
| SM (1) | SMT201400033B (https=) |
| WO (1) | WO2011042466A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2308484A1 (en) * | 2009-10-06 | 2011-04-13 | Dompé S.p.a. | Inhibitors of cxcr1/2 as adjuvants in the transplant of pancreatic islets |
| EP2308485A1 (en) * | 2009-10-06 | 2011-04-13 | Dompé S.p.a. | Sulfonamides for the prevention of diabetes |
| CN103159652B (zh) * | 2011-12-19 | 2016-06-08 | 天津市国际生物医药联合研究院 | 亚磺酰胺类化合物的制备及其应用 |
| WO2014205127A2 (en) | 2013-06-18 | 2014-12-24 | New York University | Cellular factors involved in the cytotoxicity of staphylococcus aureus leukocidins: novel therapeutic targets |
| US11291641B2 (en) * | 2016-10-03 | 2022-04-05 | The Children's Medical Center Corporation | Prevention and treatment of diabetic nephropathy |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1303249B1 (it) | 1998-10-23 | 2000-11-06 | Dompe Spa | Alcune n-(2-aril-propionil)-solfonammidi e preparazionifarmaceutiche che le contengono. |
| AU2001253496A1 (en) * | 2000-04-14 | 2001-10-30 | Millennium Pharmaceuticals, Inc. | Treating graft rejection with cxcr3 inhibitors |
| US20020042370A1 (en) * | 2000-04-14 | 2002-04-11 | Millennium Pharmaceuticals, Inc. | Method of treating graft rejection using inhibitors of CCR2 function |
| ITMI20010206A1 (it) * | 2001-02-02 | 2002-08-02 | Dompe Spa | Uso della metansolfonammide di (r)-ibuprofene e dei suoi sali non tossici per la preparazione di medicamenti per il trattamento e la prevenz |
| ATE444286T1 (de) | 2004-03-23 | 2009-10-15 | Dompe Pha R Ma Spa Res & Mfg | 2-phenylpropionsäurederivate und diese enthaltende pharmazeutische zusammensetzung |
| PT1579859E (pt) | 2004-03-25 | 2007-03-30 | Dompe Pha R Ma Spa Res & Mfg | Utilização de n-(2-aril-propionil)-sulfonamidas pata o tratamento de lesões da medula espinal |
| US20050261762A1 (en) * | 2004-05-21 | 2005-11-24 | Medtronic Vascular, Inc. | Medical devices to prevent or inhibit restenosis |
| EP1790637B1 (en) * | 2004-09-13 | 2014-01-29 | Ono Pharmaceutical Co., Ltd. | Derivatives of N-4-piperidyl urea and medicaments containing them as active ingredient |
| JP5232144B2 (ja) * | 2006-06-28 | 2013-07-10 | サノフイ | Ｃｘｃｒ２阻害剤 |
| WO2008039876A1 (en) * | 2006-09-26 | 2008-04-03 | Case Western Reserve University | Cytokine signaling |
| CN102088993A (zh) | 2008-03-20 | 2011-06-08 | 卡罗勒斯治疗公司 | 炎症的治疗方法 |
| EP2308484A1 (en) * | 2009-10-06 | 2011-04-13 | Dompé S.p.a. | Inhibitors of cxcr1/2 as adjuvants in the transplant of pancreatic islets |
-
2009
- 2009-10-06 EP EP09172364A patent/EP2308484A1/en not_active Withdrawn
-
2010
- 2010-10-06 ME MEP-2014-24A patent/ME01719B/me unknown
- 2010-10-06 PT PT107610180T patent/PT2485723E/pt unknown
- 2010-10-06 PL PL10761018T patent/PL2485723T3/pl unknown
- 2010-10-06 NZ NZ599172A patent/NZ599172A/en not_active IP Right Cessation
- 2010-10-06 ES ES10761018.0T patent/ES2451349T3/es active Active
- 2010-10-06 AU AU2010305385A patent/AU2010305385B2/en not_active Ceased
- 2010-10-06 WO PCT/EP2010/064921 patent/WO2011042466A1/en not_active Ceased
- 2010-10-06 SI SI201030553T patent/SI2485723T1/sl unknown
- 2010-10-06 CN CN201510089937.5A patent/CN104906572A/zh active Pending
- 2010-10-06 JP JP2012532579A patent/JP5834010B2/ja not_active Expired - Fee Related
- 2010-10-06 RS RS20140102A patent/RS53249B/sr unknown
- 2010-10-06 DK DK10761018.0T patent/DK2485723T3/en active
- 2010-10-06 CN CN201080045208.5A patent/CN102665703B/zh not_active Expired - Fee Related
- 2010-10-06 KR KR1020127010732A patent/KR101759362B1/ko not_active Expired - Fee Related
- 2010-10-06 HR HRP20140202AT patent/HRP20140202T1/hr unknown
- 2010-10-06 KR KR1020177015626A patent/KR101817912B1/ko not_active Expired - Fee Related
- 2010-10-06 CA CA2775902A patent/CA2775902C/en not_active Expired - Fee Related
- 2010-10-06 US US13/500,544 patent/US20120202884A1/en not_active Abandoned
- 2010-10-06 MX MX2012004082A patent/MX2012004082A/es active IP Right Grant
- 2010-10-06 EP EP10761018.0A patent/EP2485723B1/en active Active
- 2010-10-06 EA EA201270513A patent/EA021298B1/ru unknown
- 2010-10-06 BR BR112012007991A patent/BR112012007991B8/pt not_active IP Right Cessation
-
2012
- 2012-04-04 IL IL219037A patent/IL219037A/en active IP Right Grant
-
2014
- 2014-03-07 CY CY20141100185T patent/CY1115018T1/el unknown
- 2014-03-19 SM SM201400033T patent/SMT201400033B/xx unknown
-
2015
- 2015-04-06 JP JP2015077750A patent/JP6097328B2/ja not_active Expired - Fee Related
-
2016
- 2016-02-18 HK HK16101720.7A patent/HK1213777A1/zh unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101650264B1 (ko) | 보체 활성을 저해함으로써 동종이식편의 생존 연장 | |
| ES2451349T3 (es) | Inhibidores de CXCR1/2 como adyuvantes en el trasplante de islotes pancreáticos | |
| ES2528362T3 (es) | Prolongación de la supervivencia de un aloinjerto por inhibición de la actividad del complemento | |
| US20220249595A1 (en) | Compositions and methods for treating acute radiation syndrome | |
| Chang et al. | Ex-vivo generation of drug-eluting islets improves transplant outcomes by inhibiting TLR4-Mediated NFkB upregulation | |
| US20170239329A1 (en) | Therapeutic composition comprising annexin v | |
| Waegell et al. | A420983, a novel, small molecule inhibitor of LCK prevents allograft rejection | |
| ES2738500T3 (es) | Formulaciones de ácido desoxicólico y sales del mismo | |
| JP2008520682A (ja) | ヒストンデアセチラーゼ阻害剤およびその使用方法 | |
| JP7121418B2 (ja) | 局所的な虚血－再灌流により誘発される細胞死の新型なアミノチオールによる減少 | |
| ES2371635T3 (es) | Combinación de un derivado de diamida y agentes inmunosupresores para inhibir el rechazo de transplantes. | |
| WO2015084706A1 (en) | Intra-articular formulations and methods for treatment of osteoarthritis | |
| HK1175993B (en) | Inhibitors of cxcr1/2 as adjuvants in the transplant of pancreatic islets | |
| ES2362489T3 (es) | Método para usar eficazmente un medicamento y método concerniente a la prevención de efectos secundarios. | |
| Perkins | A new clinical method to measure hepatic microcirculation | |
| Carella et al. | Metabolic Disorders in Elderly Patients with Hematologic Malignancies. A Review | |
| JP2007238466A (ja) | 虚血再灌流による内臓障害の抑制剤 |