IL139956A0 - Conformationally constrained backbone cyclized somatostatin analogs - Google Patents
Conformationally constrained backbone cyclized somatostatin analogsInfo
- Publication number
- IL139956A0 IL139956A0 IL13995699A IL13995699A IL139956A0 IL 139956 A0 IL139956 A0 IL 139956A0 IL 13995699 A IL13995699 A IL 13995699A IL 13995699 A IL13995699 A IL 13995699A IL 139956 A0 IL139956 A0 IL 139956A0
- Authority
- IL
- Israel
- Prior art keywords
- somatostatin analogs
- conformationally constrained
- backbone cyclized
- disclosed
- constrained backbone
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/655—Somatostatins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/655—Somatostatins
- C07K14/6555—Somatostatins at least 1 amino acid in D-form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R31/00—Arrangements for testing electric properties; Arrangements for locating electric faults; Arrangements for electrical testing characterised by what is being tested not provided for elsewhere
- G01R31/28—Testing of electronic circuits, e.g. by signal tracer
- G01R31/317—Testing of digital circuits
- G01R31/3181—Functional testing
- G01R31/31816—Soft error testing; Soft error rate evaluation; Single event testing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R31/00—Arrangements for testing electric properties; Arrangements for locating electric faults; Arrangements for electrical testing characterised by what is being tested not provided for elsewhere
- G01R31/28—Testing of electronic circuits, e.g. by signal tracer
- G01R31/317—Testing of digital circuits
- G01R31/3181—Functional testing
- G01R31/3185—Reconfiguring for testing, e.g. LSSD, partitioning
- G01R31/318533—Reconfiguring for testing, e.g. LSSD, partitioning using scanning techniques, e.g. LSSD, Boundary Scan, JTAG
- G01R31/318541—Scan latches or cell details
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Endocrinology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Obesity (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/100,360 US6051554A (en) | 1995-06-07 | 1998-06-19 | Conformationally constrained backbone cyclized somatostatin analogs |
US09/203,389 US6355613B1 (en) | 1996-07-31 | 1998-12-02 | Conformationally constrained backbone cyclized somatostatin analogs |
PCT/IL1999/000329 WO1999065508A1 (fr) | 1998-06-19 | 1999-06-15 | Analogues de la somatostatine cyclises par squelette a contrainte de conformation |
Publications (1)
Publication Number | Publication Date |
---|---|
IL139956A0 true IL139956A0 (en) | 2002-02-10 |
Family
ID=26797065
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL13995699A IL139956A0 (en) | 1998-06-19 | 1999-06-15 | Conformationally constrained backbone cyclized somatostatin analogs |
Country Status (14)
Country | Link |
---|---|
US (3) | US6355613B1 (fr) |
EP (1) | EP1085896B1 (fr) |
JP (1) | JP4637352B2 (fr) |
KR (1) | KR100689402B1 (fr) |
AT (1) | ATE362371T1 (fr) |
AU (1) | AU747515B2 (fr) |
CA (1) | CA2335488C (fr) |
CY (1) | CY1106781T1 (fr) |
DE (1) | DE69936100T2 (fr) |
DK (1) | DK1085896T3 (fr) |
ES (1) | ES2288029T3 (fr) |
IL (1) | IL139956A0 (fr) |
NZ (1) | NZ508956A (fr) |
WO (1) | WO1999065508A1 (fr) |
Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6841533B1 (en) | 1995-12-07 | 2005-01-11 | Peptor Limited | Conformationally constrained backbone cyclized interleukin-6 antagonists |
US6355613B1 (en) * | 1996-07-31 | 2002-03-12 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
CA2284459C (fr) | 1999-10-04 | 2012-12-11 | Neokimia Inc. | Synthese combinatoire de bibliotheques de composes macrocycliques utiles pour la decouverte de medicaments |
GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
AU2001288847A1 (en) * | 2000-09-07 | 2002-03-22 | Biosyntema Inc. | Conformationally constrained labeled peptides for imaging and therapy |
US7084117B2 (en) * | 2001-01-12 | 2006-08-01 | Societe De Conseils De Recherches Et D'applications Scientifiques, Sas | Pharmaceutical compositions which inhibit vascular proliferation and method of use thereof |
DE60226419D1 (de) * | 2001-03-08 | 2008-06-19 | Univ Tulane | Somatostatin-antagonisten |
MXPA03009048A (es) * | 2001-04-09 | 2004-02-12 | Univ Tulane | Agonistas de la somatostatina. |
EP1283216A1 (fr) * | 2001-08-10 | 2003-02-12 | Mallinckrodt Inc. | Analogues de la somatostatine réagissants avec tous les différents types de récepteurs de la somatostatine |
AU2002359359A1 (en) * | 2001-12-28 | 2003-07-24 | Somatocor Pharmaceuticals, Inc. | Imidazolidin-2,4-dione derivatives as non-peptide somatostatin receptor ligands |
IL148921A0 (en) * | 2002-03-26 | 2002-09-12 | Peptor Ltd | Photo active backbone cyclized somatostatin analogs for optical imaging and photodynamic therapy |
IL150384A0 (en) * | 2002-06-24 | 2002-12-01 | Peptor Ltd | Radiolabelled somatostatin analogs backbone cyclized through metal complexation |
JP4928263B2 (ja) | 2003-07-31 | 2012-05-09 | トランザイム・ファーマ | ペプチド結合サロゲートを組み入れた空間的に規定された大環状分子 |
GB0318682D0 (en) | 2003-08-08 | 2003-09-10 | Novartis Ag | Organic compounds |
ITFI20040057A1 (it) * | 2004-03-10 | 2004-06-10 | Mauro Giuntini | Analoghi della somatostatina |
US20050287557A1 (en) * | 2004-05-10 | 2005-12-29 | Suad Efendic | Methods for identifying compounds for treating diabetes mellitus |
US20070025910A1 (en) | 2005-07-29 | 2007-02-01 | Norenberg Jeffrey P | Anticancer therapy |
WO2007093999A1 (fr) * | 2006-02-15 | 2007-08-23 | Intec Pharma Ltd. | Système de gastro-rétention pour dé livrer des macromolécules |
CN1904150B (zh) * | 2006-08-01 | 2010-07-28 | 华东师范大学 | 一种人胰高血糖素样肽-1衍生物及其固相化学合成 |
RU2010114039A (ru) * | 2007-09-11 | 2011-10-20 | Мондобайотек Лабораториз Аг (Li) | Применение октреотида в качестве терапевтического средства |
WO2011024175A1 (fr) | 2009-08-28 | 2011-03-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Composés macrocycliques, compositions associées et méthodes de prévention ou de traitement d'une infection par le vih |
EP2604281B1 (fr) * | 2011-12-14 | 2014-07-30 | Centre National de la Recherche Scientifique (CNRS) | Analogues conjugués de somatostatine coupés pour des applications biologiques |
WO2013111129A1 (fr) | 2012-01-23 | 2013-08-01 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Hélices peptidiques stabilisées pour l'inhibition de la dimérisation du récepteur 2 de chimiokine de motif c (ccr2) |
US9371282B2 (en) | 2013-05-17 | 2016-06-21 | Centrexion Therapeutics Corporation | Somatostatin receptor subtype 4 (SSTR4) agonists |
WO2015087334A1 (fr) | 2013-12-15 | 2015-06-18 | Yissum Research Develoment Company Of The Hebrew University Of Jerusalem Ltd. | Peptides dérivés de vipéristatine et leurs utilisations |
EP3135686A1 (fr) * | 2015-08-28 | 2017-03-01 | Latvian Biomedical Research and Study Centre | Nouvelle hormone de croissance humaine recombinante cyclisée |
EP3405429B1 (fr) * | 2016-01-21 | 2021-07-28 | Ramot at Tel-Aviv University Ltd. | Formation de nanoparticules fonctionnalisées par co-assemblage supramoléculaire |
WO2017141106A1 (fr) * | 2016-02-16 | 2017-08-24 | Strongbridge Biopharma plc | Veldoréotide de faible solubilité dans des conditions physiologiques destiné à être utilisé dans le traitement d'une acromégalie, d'un cancer associé à une acromégalie, de tumeurs exprimant le sst-r5, du diabète de type 2, d'une hyperglycémie, et de tumeurs associées aux hormones |
WO2017212477A1 (fr) | 2016-06-07 | 2017-12-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Peptides inhibiteurs à squelette cyclisé du facteur de différenciation myéloïde 88 (myd88) |
US11261215B2 (en) | 2017-09-19 | 2022-03-01 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Somatostatin prodrugs |
EP3927737A1 (fr) | 2019-02-21 | 2021-12-29 | Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. | Peptides dérivés de par4, analogues et leurs utilisations |
WO2022003673A1 (fr) | 2020-06-30 | 2022-01-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Analogues de l'humanine et leurs utilisations |
AR127055A1 (es) | 2021-09-14 | 2023-12-13 | Lilly Co Eli | Sales agonistas de sstr4 |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4011182A (en) | 1975-03-21 | 1977-03-08 | American Home Products Corporation | Cyclic undecapeptide analogs of somatostatin and intermediates |
US3988304A (en) | 1975-08-25 | 1976-10-26 | American Home Products Corporation | Cyclic dodecapeptide derivatives of somatostatin and intermediates thereof |
US4054558A (en) | 1976-05-24 | 1977-10-18 | American Home Products Corporation | Cyclic dodecapeptide and intermediates therefor |
SU798098A1 (ru) | 1977-12-14 | 1981-01-23 | Ордена Трудового Красного Знамениинститут Органического Синтезаан Латвийской Ccp | Циклический аналог брадикинина,обла-дАющий СпОСОбНОСТью СОздАВАТь пРОлОНги-РОВАННый дЕпРЕССОРНый эффЕКТ B эКСпЕРиМЕН-TE ,A ТАКжЕ ВАСКул РНую пРОНи-цАЕМОСТь B эКСпЕРиМЕНТЕ |
US4191754A (en) | 1979-02-28 | 1980-03-04 | Merck & Co., Inc. | Bicyclic somatostatin analogs |
US4235886A (en) | 1979-10-31 | 1980-11-25 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
US4310518A (en) | 1979-10-31 | 1982-01-12 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
ATE2512T1 (de) * | 1979-11-27 | 1983-03-15 | Sandoz Ag | Polypeptide, verfahren zu ihrer herstellung, pharmazeutische zusammensetzungen, die diese polypeptide enthalten, und ihre verwendung. |
US4369179A (en) * | 1979-12-14 | 1983-01-18 | Ciba-Geigy Corporation | Acylpeptides |
DE3845000C2 (de) | 1987-07-10 | 1998-11-19 | Novartis Ag | Anwendung von Octreotid zur Behandlung von Brustkrebs |
US4923963A (en) | 1987-09-02 | 1990-05-08 | Nova Technology Limited Partnership | Bradykinin antagonist peptides |
US5073541A (en) | 1987-11-18 | 1991-12-17 | Administrators Of The Tulane Educational Fund | Treatment of small cell lung cancer with somatostatin analogs |
EP0334244A3 (fr) | 1988-03-25 | 1991-05-29 | The Procter & Gamble Company | Peptides antagonistes de Bradykinine |
AU3534989A (en) | 1988-04-08 | 1989-11-03 | Scripps Clinic And Research Foundation | Polypeptides stabilized by covalent hydrogen bond replacements |
IE63490B1 (en) | 1988-11-24 | 1995-05-03 | Hoechst Ag | Peptides having bradykinin antagonist action |
US5753627A (en) | 1988-12-05 | 1998-05-19 | Novartis Ag | Use of certain complexed somatostatin peptides for the invivo imaging of somatostatin receptor-positive tumors and metastasis |
US5650489A (en) | 1990-07-02 | 1997-07-22 | The Arizona Board Of Regents | Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof |
HU207104B (en) | 1991-01-25 | 1993-03-01 | Biosignal Kutato Fejlesztoe Kf | Process for producing new somatostatin analogs inhibiting tumour growth and pharmaceutical compositions comprising such compounds |
CA2102633A1 (fr) | 1991-06-03 | 1992-12-04 | Peter H. Cox | Derives radiomarques de la somatostatine, leur preparation et leur utilisation |
DE4119544C1 (fr) | 1991-06-13 | 1992-10-15 | Gesellschaft Fuer Biotechnologische Forschung Mbh (Gbf), 3300 Braunschweig, De | |
US5364851A (en) | 1991-06-14 | 1994-11-15 | International Synthecon, Llc | Conformationally restricted biologically active peptides, methods for their production and uses thereof |
US5225180A (en) | 1991-09-10 | 1993-07-06 | Diatech, Inc. | Technetium-99m labeled somatostatin-derived peptides for imaging |
US6117974A (en) * | 1991-10-02 | 2000-09-12 | Peptor Limited | Libraries of backbone-cyclized peptidomimetics |
IL99628A (en) | 1991-10-02 | 2004-07-25 | Yissum Res Dev Co | Processes for the preparation of cyclic peptides, and pharmaceutical compositions containing them |
ATE203417T1 (de) | 1992-02-05 | 2001-08-15 | Mallinckrodt Inc | Radioaktiv markierte somatostatin |
US5411943A (en) | 1992-02-25 | 1995-05-02 | Biomeasure, Inc. | Hepatoma treatment with somatostatin analogs |
US5620675A (en) | 1992-06-23 | 1997-04-15 | Diatech, Inc. | Radioactive peptides |
US5371070A (en) | 1992-11-09 | 1994-12-06 | The Salk Institute For Biological Studies | Bicyclic GnRH antagonists and a method for regulating the secretion of gonadotropins |
EP0607103A3 (fr) | 1993-01-12 | 1997-07-09 | Sandoz Ltd | Analogues de somatostatine contenants des agents de chélation et leur compositions radio-marquées. |
EP1099707A3 (fr) * | 1993-06-23 | 2002-01-09 | Diatide, Inc. | Peptides derives de la somatostatine et marques de maniere radioactive pour imagerie et utilisations therapeutiques |
US5449761A (en) | 1993-09-28 | 1995-09-12 | Cytogen Corporation | Metal-binding targeted polypeptide constructs |
IL109943A (en) | 1994-06-08 | 2006-08-01 | Develogen Israel Ltd | Conformationally constrained backbone cyclized peptide analogs |
US5597894A (en) | 1995-06-05 | 1997-01-28 | The Louisiana State University Medical Center Foundation | Multi-tyrosinated somatostatin analogs |
US6051554A (en) * | 1995-06-07 | 2000-04-18 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
US5770687A (en) * | 1995-06-07 | 1998-06-23 | Peptor Limited | Comformationally constrained backbone cyclized somatostatin analogs |
US6355613B1 (en) * | 1996-07-31 | 2002-03-12 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
US6025372A (en) | 1997-04-04 | 2000-02-15 | Merck & Co., Inc. | Somatostatin agonists |
US6335613B1 (en) * | 2000-12-04 | 2002-01-01 | Abb T&D Technology Ltd. | Versatile power flow transformers for compensating power flow in a transmission line |
-
1998
- 1998-12-02 US US09/203,389 patent/US6355613B1/en not_active Expired - Lifetime
-
1999
- 1999-06-15 AT AT99957020T patent/ATE362371T1/de active
- 1999-06-15 JP JP2000554387A patent/JP4637352B2/ja not_active Expired - Fee Related
- 1999-06-15 KR KR1020007014431A patent/KR100689402B1/ko not_active IP Right Cessation
- 1999-06-15 AU AU42884/99A patent/AU747515B2/en not_active Ceased
- 1999-06-15 CA CA2335488A patent/CA2335488C/fr not_active Expired - Lifetime
- 1999-06-15 IL IL13995699A patent/IL139956A0/xx unknown
- 1999-06-15 NZ NZ508956A patent/NZ508956A/xx not_active IP Right Cessation
- 1999-06-15 ES ES99957020T patent/ES2288029T3/es not_active Expired - Lifetime
- 1999-06-15 WO PCT/IL1999/000329 patent/WO1999065508A1/fr active IP Right Grant
- 1999-06-15 EP EP99957020A patent/EP1085896B1/fr not_active Expired - Lifetime
- 1999-06-15 DK DK99957020T patent/DK1085896T3/da active
- 1999-06-15 DE DE69936100T patent/DE69936100T2/de not_active Expired - Lifetime
-
2000
- 2000-12-13 US US09/734,583 patent/US6930088B2/en not_active Expired - Fee Related
-
2004
- 2004-08-12 US US10/916,522 patent/US7060679B2/en not_active Expired - Lifetime
-
2007
- 2007-08-01 CY CY20071101021T patent/CY1106781T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
ES2288029T3 (es) | 2007-12-16 |
US20020052315A1 (en) | 2002-05-02 |
EP1085896A4 (fr) | 2005-04-06 |
EP1085896B1 (fr) | 2007-05-16 |
WO1999065508A1 (fr) | 1999-12-23 |
DE69936100D1 (de) | 2007-06-28 |
NZ508956A (en) | 2003-06-30 |
US6355613B1 (en) | 2002-03-12 |
US6930088B2 (en) | 2005-08-16 |
CA2335488A1 (fr) | 1999-12-23 |
JP4637352B2 (ja) | 2011-02-23 |
EP1085896A1 (fr) | 2001-03-28 |
CA2335488C (fr) | 2011-08-23 |
AU747515B2 (en) | 2002-05-16 |
ATE362371T1 (de) | 2007-06-15 |
US20050043226A1 (en) | 2005-02-24 |
US7060679B2 (en) | 2006-06-13 |
KR100689402B1 (ko) | 2007-03-08 |
JP2002518339A (ja) | 2002-06-25 |
KR20010071523A (ko) | 2001-07-28 |
CY1106781T1 (el) | 2012-05-23 |
AU4288499A (en) | 2000-01-05 |
DK1085896T3 (da) | 2007-09-10 |
DE69936100T2 (de) | 2008-02-07 |
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