RU2014134409A - Конъюгаты этопозида и доксорубицина для доставки лекарственных средств - Google Patents

Конъюгаты этопозида и доксорубицина для доставки лекарственных средств Download PDF

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RU2014134409A
RU2014134409A RU2014134409A RU2014134409A RU2014134409A RU 2014134409 A RU2014134409 A RU 2014134409A RU 2014134409 A RU2014134409 A RU 2014134409A RU 2014134409 A RU2014134409 A RU 2014134409A RU 2014134409 A RU2014134409 A RU 2014134409A
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Мишель ДЕМОЛЕ
Кристиан ЧЕ
Райнхард ГАБАТУЛЕР
Гаоцян ЯНГ
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Ангиокем Инк.
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Abstract

1. Соединение, имеющее структуру,где Y представляет собой гидролизуемый линкер;или его фармацевтически приемлемая соль.2. Соединение по п. 1, где Y имеет структуру:где каждый G и G′ представляет собой, независимо, -С(O)-, -С(O)O-, -ОС(O)-, -S(O)O-, -OS(O)-, -S(O)NH-, -NHS(O)-, или -OP(O)(OR)O-;X представляет собой -(необязательно замещенный арил)-, -(CRR)-, -O{(CRR)O}-, -{(CRR)O(CRR)}-, или -(CRR)R(CRR)-;каждый n, о, и р представляет собой, независимо, 1, 2, 3, 4, 5, 6, 7, 8, 9, или 10;Rпредставляет собой Н или Cалкил;Rи Rкаждый независимо выбран из Н, ОН, или Cалкила; иRпредставляет собой О, NH, N(Cалкил), или -необязательно замещенный арил.3. Соединение по п. 2, где G представляет собой -С(O)-.4. Соединение по п. 2 или 3, где G′ представляет собой -С(O)-.5. Соединение по п. 2, где Х представляет собой -(CRR)-.6. Соединение по п. 5, где n представляет собой 1, 2, 3, 4, 5 или 6.7. Соединение по п. 6, где n представляет собой 2 или 3.8. Соединение по п. 7, где n представляет собой 3.9. Фармацевтическая композиция, содержащая соединение по любому из п.п. 1-8 и фармацевтически приемлемый носитель.10. Способ лечения рака, включающий введение пациенту терапевтически эффективного количества соединения по любому из пп. 1-8 или фармацевтической композиции по п. 9.11. Способ по п. 10, дополнительно включающий введение второго терапевтического агента.12. Способ по п. 11, где второй терапевтический агент представляет собой полипептид, включающий последовательность Angiopep-2 (SEQ ID NO:97), и где Angiopep-2 конъюгирован с противораковым агентом.13. Способ по п. 12, где противораковый агент представляет собой паклитаксел.14. Способ по п. 13, где второй терапевтический агент представляет собой ANG1005, имеющий следующую структуру:.

Claims (14)

1. Соединение, имеющее структуру
Figure 00000001
,
где Y представляет собой гидролизуемый линкер;
или его фармацевтически приемлемая соль.
2. Соединение по п. 1, где Y имеет структуру:
Figure 00000002
где каждый G и G′ представляет собой, независимо, -С(O)-, -С(O)O-, -ОС(O)-, -S(O)2O-, -OS(O)2-, -S(O)2NH-, -NHS(O)2-, или -OP(O)(OR11)O-;
X представляет собой -(необязательно замещенный арил)-, -(CR12R13)n-, -O{(CR12R13)2O}n-, -{(CR12R13)2O(CR12R13)2}n-, или -(CR12R13)oR14(CR12R13)p-;
каждый n, о, и р представляет собой, независимо, 1, 2, 3, 4, 5, 6, 7, 8, 9, или 10;
R11 представляет собой Н или C1-6 алкил;
R12 и R13 каждый независимо выбран из Н, ОН, или C1-6 алкила; и
R14 представляет собой О, NH, N(C1-6 алкил), или -необязательно замещенный арил.
3. Соединение по п. 2, где G представляет собой -С(O)-.
4. Соединение по п. 2 или 3, где G′ представляет собой -С(O)-.
5. Соединение по п. 2, где Х представляет собой -(CR12R13)n-.
6. Соединение по п. 5, где n представляет собой 1, 2, 3, 4, 5 или 6.
7. Соединение по п. 6, где n представляет собой 2 или 3.
8. Соединение по п. 7, где n представляет собой 3.
9. Фармацевтическая композиция, содержащая соединение по любому из п.п. 1-8 и фармацевтически приемлемый носитель.
10. Способ лечения рака, включающий введение пациенту терапевтически эффективного количества соединения по любому из пп. 1-8 или фармацевтической композиции по п. 9.
11. Способ по п. 10, дополнительно включающий введение второго терапевтического агента.
12. Способ по п. 11, где второй терапевтический агент представляет собой полипептид, включающий последовательность Angiopep-2 (SEQ ID NO:97), и где Angiopep-2 конъюгирован с противораковым агентом.
13. Способ по п. 12, где противораковый агент представляет собой паклитаксел.
14. Способ по п. 13, где второй терапевтический агент представляет собой ANG1005, имеющий следующую структуру:
Figure 00000003
.
RU2014134409A 2008-10-15 2014-08-22 Конъюгаты этопозида и доксорубицина для доставки лекарственных средств RU2014134409A (ru)

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Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1583562T3 (da) 2003-01-06 2011-09-19 Angiochem Inc Angiopep-1, beslægtede forbindelser og anvendelser deraf
ES2383901T5 (es) 2005-02-18 2015-02-25 Angiochem Inc. Polipéptidos de aprotinina para transportar un compuesto a través de la barrera sangre-cerebro
US20090016959A1 (en) * 2005-02-18 2009-01-15 Richard Beliveau Delivery of antibodies to the central nervous system
ES2424242T3 (es) 2005-07-15 2013-09-30 Angiochem Inc. Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos
EP2074142A4 (en) 2006-10-19 2010-10-27 Angiochem Inc COMPOUNDS FOR STIMULATING THE FUNCTION OF P-GLYCOPROTEIN AND APPLICATIONS THEREOF
US9365634B2 (en) 2007-05-29 2016-06-14 Angiochem Inc. Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues
BRPI0920209A2 (pt) 2008-10-15 2015-12-22 Angiochem Inc conjugados de agonistas de glp-1 e usos dos mesmos
RU2531591C2 (ru) 2008-10-15 2014-10-20 Ангиокем Инк. Конъюгаты этопозида и доксорубицина для доставки лекарственных средств
US9914754B2 (en) 2008-12-05 2018-03-13 Angiochem Inc. Conjugates of neurotensin or neurotensin analogs and uses thereof
MX2011006685A (es) 2008-12-17 2011-09-27 Angiochem Inc Inhibidores de metaloproteinas de matriz de membrana tipo-1 y sus usos.
ES2729261T3 (es) 2009-04-20 2019-10-31 Angiochem Inc Tratamiento del cáncer de ovario utilizando un agente anticancerígeno conjugado con un análogo de Angiopep-2
IN2012DN00248A (ru) 2009-07-02 2015-05-01 Angiochem Inc
EP2885318A4 (en) 2012-08-14 2016-03-30 Angiochem Inc PEPTIDE-DENDRIMER CONJUGATES AND USES THEREOF
CA2894548C (en) * 2012-12-13 2021-01-12 Cytrx Corporation Anthracycline formulations
NZ631022A (en) 2013-06-05 2018-05-25 Cytrx Corp Cytotoxic agents for the treatment of cancer
ES2826827T3 (es) * 2015-06-15 2021-05-19 Angiochem Inc Métodos para el tratamiento de carcinomatosis leptomeníngea
CN111718395B (zh) * 2019-03-21 2022-03-18 国家纳米科学中心 一种前药激活化合物、前药体系及其制备方法和应用
CN110590877B (zh) * 2019-08-13 2021-02-19 南开大学 连接子，载药连接子、细胞穿透肽偶联药物、抗体偶联药物及其制备方法
WO2023220641A2 (en) 2022-05-11 2023-11-16 Juno Therapeutics, Inc. Methods and uses related to t cell therapy and production of same

Family Cites Families (147)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4671958A (en) 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
US4902505A (en) 1986-07-30 1990-02-20 Alkermes Chimeric peptides for neuropeptide delivery through the blood-brain barrier
US4801575A (en) 1986-07-30 1989-01-31 The Regents Of The University Of California Chimeric peptides for neuropeptide delivery through the blood-brain barrier
US4904768A (en) 1987-08-04 1990-02-27 Bristol-Myers Company Epipodophyllotoxin glucoside 4'-phosphate derivatives
GB2208511A (en) 1987-08-07 1989-04-05 Bayer Ag Variants of bovine pancreatic trypsin inhibitor produced by recombinant dna technology
US4942184A (en) 1988-03-07 1990-07-17 The United States Of America As Represented By The Department Of Health And Human Services Water soluble, antineoplastic derivatives of taxol
US5632990A (en) 1988-04-22 1997-05-27 Cancer Research Campaign Tech. Ltd. Treatment for tumors comprising conjugated antibody A5B7 and a prodrug
US5258499A (en) 1988-05-16 1993-11-02 Vestar, Inc. Liposome targeting using receptor specific ligands
US5028697A (en) 1988-08-08 1991-07-02 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized methotrexate analogs via simple organic linkers
US5169933A (en) 1988-08-15 1992-12-08 Neorx Corporation Covalently-linked complexes and methods for enhanced cytotoxicity and imaging
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5948634A (en) 1988-12-21 1999-09-07 The General Hospital Coporation Neural thread protein gene expression and detection of alzheimer's disease
DE3912638A1 (de) 1989-04-18 1990-10-31 Bayer Ag Gentechnologisch hergestellte homologe des alzheimer protease inhibitors, wirtstaemme sowie expressionsvektoren fuer ihre herstellung und ihre verwendung als arzneimittel
US5126249A (en) 1989-05-09 1992-06-30 Eli Lilly And Company Enzymatic removal of a protein amino-terminal sequence
US6020145A (en) 1989-06-30 2000-02-01 Bristol-Myers Squibb Company Methods for determining the presence of carcinoma using the antigen binding region of monoclonal antibody BR96
US6475781B1 (en) 1990-05-17 2002-11-05 Dana-Farber Cancer Institute, Inc. Trans-dominant suppressor genes for oligomeric proteins
GB9017008D0 (en) 1990-08-02 1990-09-19 Erba Carlo Spa Process for the enzymatic preparation of basic fibroblast growth factor
US5714167A (en) 1992-06-15 1998-02-03 Emisphere Technologies, Inc. Active agent transport systems
US6495513B1 (en) 1991-03-11 2002-12-17 Curis, Inc. Morphogen-enhanced survival and repair of neural cells
US5955444A (en) 1991-08-09 1999-09-21 Massachusetts Institute Of Technology Method of inhibiting abnormal tau hyper phosphorylation in a cell
US5627270A (en) 1991-12-13 1997-05-06 Trustees Of Princeton University Glycosylated steroid derivatives for transport across biological membranes and process for making and using same
US5204354A (en) 1992-02-14 1993-04-20 Merck & Co., Inc. Substituted quinazolinones as neurotensin antagonists useful in the treatment of CNS disorders
GB9213077D0 (en) 1992-06-19 1992-08-05 Erba Carlo Spa Polymerbound taxol derivatives
EP0671944A4 (en) 1992-09-25 1996-07-24 Corvas Int Inc TISSUE VIA-THROMBOPLASTIN FACTOR COMPLEX INHIBITORS DERIVED FROM A BOVINE PANCREATIC TRYPSIN INHIBITOR.
EP0599303A3 (en) 1992-11-27 1998-07-29 Takeda Chemical Industries, Ltd. Peptide conjugate
WO1994019692A1 (en) 1993-02-18 1994-09-01 The General Hospital Corporation Alzheimer's disease therapeutics
ZA963619B (en) 1995-05-08 1996-11-22 Scios Inc Protease inhibitor peptides
US5780265A (en) 1995-06-05 1998-07-14 Genentech, Inc. Kunitz type plasma kallikrein inhibitors
US5665702A (en) 1995-06-06 1997-09-09 Biomeasure Incorporated Ionic molecular conjugates of N-acylated derivatives of poly(2-amino-2-deoxy-D-glucose) and polypeptides
IL126115A (en) 1996-03-11 2007-03-08 Aerovance Inc Significantly purified protein with suppressive activity for sirin protease and its pharmaceutical preparations
DE19636889A1 (de) 1996-09-11 1998-03-12 Felix Dr Kratz Antineoplastisch wirkende Transferrin- und Albuminkonjugate zytostatischer Verbindungen aus der Gruppe der Anthrazykline, Alkylantien, Antimetabolite und Cisplatin-Analoga und diese enthaltende Arzneimittel
EP0932390A1 (en) 1996-10-11 1999-08-04 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method
US6056973A (en) 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
US5948750A (en) 1996-10-30 1999-09-07 Merck & Co., Inc. Conjugates useful in the treatment of prostate cancer
AU6682598A (en) 1997-03-04 1998-09-22 Bio-Technology General Corporation Isolation of tissue specific peptide ligands and their use for targeting pharmaceuticals to organs
GB9705903D0 (en) 1997-03-21 1997-05-07 Elliott Gillian D VP22 Proteins and uses thereof
US6126965A (en) 1997-03-21 2000-10-03 Georgetown University School Of Medicine Liposomes containing oligonucleotides
BR9809138A (pt) 1997-05-21 2001-08-28 Trustees For The Leland Stanfo Conjugado e método para aumentar o transporte de um composto selecionado atravessando uma membrana biológica
US6391305B1 (en) 1997-09-10 2002-05-21 Merck & Co., Inc. Conjugates useful in the treatment of prostate cancer
US6093692A (en) 1997-09-25 2000-07-25 The University Of Southern California Method and compositions for lipidization of hydrophilic molecules
US6475481B2 (en) 1997-11-18 2002-11-05 Canji Inc Purging of stem cell products
WO1999026657A1 (en) 1997-11-25 1999-06-03 Musc Foundation For Research Development Inhibitors of nitric oxide synthase
US5981564A (en) 1998-07-01 1999-11-09 Universite Laval Water-soluble derivatives of paclitaxel, method for producing same and uses thereof
US6703381B1 (en) 1998-08-14 2004-03-09 Nobex Corporation Methods for delivery therapeutic compounds across the blood-brain barrier
US5922754A (en) 1998-10-02 1999-07-13 Abbott Laboratories Pharmaceutical compositions containing paclitaxel
WO2000050059A1 (en) 1999-02-24 2000-08-31 The Uab Research Foundation Taxane derivatives for targeted therapy of cancer
US6180607B1 (en) 1999-08-05 2001-01-30 Christopher Davies Protein having proteinase inhibitor activity
US6713454B1 (en) 1999-09-13 2004-03-30 Nobex Corporation Prodrugs of etoposide and etoposide analogs
EP1214292B1 (en) 1999-09-24 2007-06-13 Genentech, Inc. Tyrosine derivatives
DE19953696A1 (de) 1999-11-09 2001-05-10 Alexander Cherkasky Selektive proteolytische Synzyme (SPS)
AU2001285020A1 (en) * 2000-08-17 2002-02-25 Synapse Technologies, Inc. P97-active agent conjugates and their methods of use
AU2002254400B2 (en) 2001-03-23 2007-08-09 Napro Biotherapeutics, Inc. Molecular conjugates for use in treatment of cancer
US20030170891A1 (en) 2001-06-06 2003-09-11 Mcswiggen James A. RNA interference mediated inhibition of epidermal growth factor receptor gene expression using short interfering nucleic acid (siNA)
EP2147679B1 (en) 2001-07-25 2014-06-25 Raptor Pharmaceutical, Inc. Compositions for blood-brain barrier transport
US20040161776A1 (en) 2001-10-23 2004-08-19 Maddon Paul J. PSMA formulations and uses thereof
US7192921B2 (en) 2001-11-08 2007-03-20 The Burnham Institute Peptides that home to tumor lymphatic vasculature and methods of using same
CA2474283A1 (en) 2002-02-07 2003-08-14 Yissum Research Development Company Of The Hebrew University In Jerusale M Amino acid sequences capable of facilitating penetration across a biological barrier
EP1495045B1 (en) 2002-03-29 2009-09-02 Creagene, Inc. Cytoplasmic transduction peptides and uses thereof
US6881829B2 (en) 2002-04-26 2005-04-19 Chimeracom, L.L.C. Chimeric hybrid analgesics
EP1539208A2 (en) 2002-06-28 2005-06-15 Nastech Pharmaceutical Company Inc. Compositions and methods for modulating physiology of epithelial junctional adhesion molecules for enhanced mucosal delivery of therapeutic compounds
AU2003295600A1 (en) 2002-11-14 2004-06-15 Dharmacon, Inc. Functional and hyperfunctional sirna
US7829694B2 (en) 2002-11-26 2010-11-09 Medtronic, Inc. Treatment of neurodegenerative disease through intracranial delivery of siRNA
US7319090B2 (en) 2002-11-27 2008-01-15 University Of North Carolina At Chapel Hill Methods of treating cerebral ischemia
US7388079B2 (en) 2002-11-27 2008-06-17 The Regents Of The University Of California Delivery of pharmaceutical agents via the human insulin receptor
US20040102369A1 (en) 2002-11-27 2004-05-27 The Regents Of The University Of California Transport of basic fibroblast growth factor across the blood brain barrier
DK1583562T3 (da) 2003-01-06 2011-09-19 Angiochem Inc Angiopep-1, beslægtede forbindelser og anvendelser deraf
US20040162284A1 (en) 2003-02-19 2004-08-19 Harris Herbert W. Method of lowering body temperature with (S) tofisopam
EP1615655B1 (en) 2003-04-08 2012-02-22 Biotempt B.V. Use of compositions for mucosal and oral administration comprising hcg fragments
EP1620544B1 (en) 2003-04-17 2018-09-19 Alnylam Pharmaceuticals Inc. MODIFIED iRNA AGENTS
WO2004108071A2 (en) 2003-06-05 2004-12-16 Salk Institute For Biological Studies Targeting polypeptides to the central nervous system
CA2525236C (en) 2003-06-20 2015-03-24 Biomarin Pharmaceutical Inc. Delivery of therapeutic compounds to the brain and other tissues
US20050026823A1 (en) 2003-06-20 2005-02-03 Biomarin Pharmaceutical Inc. Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues
US7927811B2 (en) 2003-08-08 2011-04-19 Proteus Sciences Co., Ltd. Polypeptides having brain-localizing activity and uses thereof
EP1663278A4 (en) 2003-08-28 2009-07-29 Biorexis Pharmaceutical Corp EPO MIMETIC PEPTIDES AND FUSION PROTEINS
US20050058702A1 (en) 2003-09-17 2005-03-17 Ben-Sasson Shmuel A. Compositions capable of facilitating penetration across a biological barrier
US20050208095A1 (en) 2003-11-20 2005-09-22 Angiotech International Ag Polymer compositions and methods for their use
US7208174B2 (en) 2003-12-18 2007-04-24 Hoffmann-La Roche Inc. Liposome compositions
KR20070039593A (ko) 2004-07-21 2007-04-12 암브룩스, 인코포레이티드 비천연적으로 코딩된 아미노산을 이용한 생합성 폴리펩티드
AU2005266184A1 (en) 2004-07-26 2006-02-02 Asterion Limited Linkers
WO2006039253A2 (en) 2004-09-29 2006-04-13 Children's Memorial Hospital Sirna-mediated gene silencing of alpha synuclein
US9002652B1 (en) 2005-01-27 2015-04-07 Institute For Systems Biology Methods for identifying and using organ-specific proteins in blood
PL1853250T3 (pl) 2005-02-18 2012-03-30 Abraxis Bioscience Llc Kombinacje i sposoby podawania środków terapeutycznych oraz terapia skojarzona
ES2383901T5 (es) * 2005-02-18 2015-02-25 Angiochem Inc. Polipéptidos de aprotinina para transportar un compuesto a través de la barrera sangre-cerebro
US20090016959A1 (en) 2005-02-18 2009-01-15 Richard Beliveau Delivery of antibodies to the central nervous system
WO2006108052A2 (en) 2005-04-06 2006-10-12 Genzyme Corporation Peg and polysialic lysosomal enzyme conjugates via acid labile linkers for therapeutic targeting
EP1888121A2 (en) 2005-05-12 2008-02-20 Tapestry Pharmaceuticals, Inc. Anticancer targeted conjugates comprising a succinyl or glutaryl linker
WO2006138343A2 (en) 2005-06-14 2006-12-28 Raptor Pharmaceutical Inc. Compositions comprising receptor - associated protein (rap) variants specific for lrp2 and uses thereof
ES2424242T3 (es) * 2005-07-15 2013-09-30 Angiochem Inc. Uso de polipéptidos de aprotinina como portadores en conjugados farmacéuticos
WO2007012004A2 (en) 2005-07-19 2007-01-25 The Board Of Trustees Of The University Of Illinois Transport agents for crossing the blood-brain barrier and into brain cancer cells, and methods of use thereof
US9062126B2 (en) 2005-09-16 2015-06-23 Raptor Pharmaceuticals Inc. Compositions comprising receptor-associated protein (RAP) variants specific for CR-containing proteins and uses thereof
US8053569B2 (en) 2005-10-07 2011-11-08 Armagen Technologies, Inc. Nucleic acids encoding and methods of producing fusion proteins
EP2202239A1 (en) 2005-11-01 2010-06-30 Alnylam Pharmaceuticals Inc. RNAI inhibition of influenza virus replication
WO2007053946A1 (en) 2005-11-09 2007-05-18 Conjuchem Biotechnologies Inc. Method of treating diabetes and/or obesity with reduced nausea side effects using an insulinotropic peptide conjugated to albumin
US8290433B2 (en) 2007-11-14 2012-10-16 Blaze Mobile, Inc. Method and system for securing transactions made through a mobile communication device
AR054215A1 (es) 2006-01-20 2007-06-13 Eriochem Sa Una formulacion farmaceutica de un taxano, una composicion solida de un taxano liofilizado a partir de una solucion de acido acetico, un procedimiento para la preparacion de dicha composicion solida de un taxano, una composicion solubilizante de un taxano liofilizado, y un conjunto de elementos (kit
US7477504B1 (en) 2006-03-13 2009-01-13 C.P.D. Technologies, Inc. Versatile stun glove
WO2008100328A2 (en) 2006-07-13 2008-08-21 Burnham Institute For Medical Research METHODS AND COMPOSITIONS FOR TARGETING gC1qR/p32
EP2074142A4 (en) 2006-10-19 2010-10-27 Angiochem Inc COMPOUNDS FOR STIMULATING THE FUNCTION OF P-GLYCOPROTEIN AND APPLICATIONS THEREOF
US9399675B2 (en) 2007-02-28 2016-07-26 The Board Of Regents Of The University Of Oklahoma Methods and compositions for diagnosing Alzheimer's disease and age-related macular degeneration
US8795627B2 (en) 2007-03-21 2014-08-05 Raptor Pharmaceuticals Inc. Treatment of liver disorders by administration of RAP conjugates
BRPI0809234A2 (pt) 2007-03-21 2014-09-02 Raptor Pharmaceutical Inc Peptídeos de proteína associada a receptor (rap) cíclico
WO2009039188A1 (en) 2007-09-17 2009-03-26 Ludwig Institute For Cancer Research Ltd Peptides and methods for the treatment of gliomas and other cancers
US8193182B2 (en) 2008-01-04 2012-06-05 Intellikine, Inc. Substituted isoquinolin-1(2H)-ones, and methods of use thereof
US20110117627A1 (en) 2008-07-10 2011-05-19 The Board Of Trustees Of The University Of Illinois Regulation of apoptosis by neural specific splice variants of ig20
RU2531591C2 (ru) 2008-10-15 2014-10-20 Ангиокем Инк. Конъюгаты этопозида и доксорубицина для доставки лекарственных средств
US9914754B2 (en) 2008-12-05 2018-03-13 Angiochem Inc. Conjugates of neurotensin or neurotensin analogs and uses thereof
MX2011006685A (es) 2008-12-17 2011-09-27 Angiochem Inc Inhibidores de metaloproteinas de matriz de membrana tipo-1 y sus usos.
US20100284921A1 (en) 2009-05-08 2010-11-11 Temple University - Of The Commonwealth System Of Higher Education Targeted nanoparticles for intracellular cancer therapy
US20110111056A1 (en) 2009-06-03 2011-05-12 Dicerna Pharmaceuticals, Inc. Peptide dicer substrate agents and methods for their specific inhibition of gene expression
ES2562463T3 (es) 2009-07-14 2016-03-04 Mayo Foundation For Medical Education And Research Administración no covalente, mediada por péptidos, de agentes activos a través de la barrera hematoencefálica
US8530429B2 (en) 2009-11-24 2013-09-10 Arch Cancer Therapeutics, Inc. Brain tumor targeting peptides and methods
US9095541B2 (en) 2009-11-24 2015-08-04 Arch Cancer Therapeutics, Inc. Brain tumor targeting peptides and methods
EP2333074A1 (en) 2009-12-14 2011-06-15 Robert Steinfeld Substances and methods for the treatment of lysosmal storage diseases
CA2789484C (en) 2010-03-08 2019-10-22 Sloan-Kettering Institute For Cancer Research Cdc7 kinase inhibitors and uses thereof
EP2550285B1 (en) 2010-03-22 2017-07-19 President and Fellows of Harvard College Trioxacarcins and uses thereof
WO2011119608A1 (en) 2010-03-26 2011-09-29 University Of Tennessee Research Foundation Peptides that specifically target amyloid deposits
EP2558503B1 (en) 2010-04-14 2015-12-09 National Research Council of Canada Compositions and methods for brain delivery of analgesic peptides
US8218280B2 (en) 2010-07-08 2012-07-10 Schneider Electric USA, Inc. Secondary thermal sensor for primary conductors
EP2601220A2 (en) 2010-08-06 2013-06-12 U3 Pharma GmbH Use of her3 binding agents in prostate treatment
CN102406949B (zh) 2010-09-21 2013-05-29 复旦大学 一种靶向示踪的多模式诊断纳米影像药物
CA2817577A1 (en) 2010-11-10 2012-05-18 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
CA2817250A1 (en) 2010-11-18 2012-05-24 The General Hospital Corporation Novel compositions and uses of anti-hypertension agents for cancer therapy
CN102552928A (zh) 2010-12-19 2012-07-11 复旦大学 一种治疗脑部肿瘤的双级靶向递药系统及其制备方法
KR101875720B1 (ko) 2011-01-10 2018-07-09 인피니티 파마슈티칼스, 인코포레이티드 이소퀴놀린온 및 이의 고체 형태의 제조 방법
CN102614105A (zh) 2011-01-28 2012-08-01 复旦大学 一种脑靶向载两性霉素b聚合物胶束给药系统
JP2014506922A (ja) 2011-03-01 2014-03-20 ティーオー − ビービービー ホールディング ベスローテン フェンノートシャップ 難水溶性物質の高度なアクティブリポソームローディング
WO2012135025A2 (en) 2011-03-28 2012-10-04 Massachusetts Institute Of Technology Conjugated lipomers and uses thereof
WO2012138694A2 (en) 2011-04-07 2012-10-11 Emory University Compositions comprising saccharide binding moieties and methods for targeted therapy
RU2013154422A (ru) 2011-05-09 2015-06-20 Институт Кимик Де Саррия Полимерные наночастицы, предназначенные для доставки лекарственных средств
WO2013004716A1 (en) 2011-07-04 2013-01-10 Universität Basel Peptide beads
KR20140063605A (ko) 2011-07-19 2014-05-27 인피니티 파마슈티칼스, 인코포레이티드 헤테로사이클릭 화합물 및 그의 용도
JP6027610B2 (ja) 2011-07-19 2016-11-16 インフィニティー ファーマシューティカルズ， インコーポレイテッド 複素環式化合物及びその使用
RU2636588C2 (ru) 2011-08-11 2017-11-24 ИНТЕЛЛАЙКИН, ЭлЭлСи Полиморфы ингибитора киназы
AR091790A1 (es) 2011-08-29 2015-03-04 Infinity Pharmaceuticals Inc Derivados de isoquinolin-1-ona y sus usos
WO2013049332A1 (en) 2011-09-29 2013-04-04 Infinity Pharmaceuticals, Inc. Inhibitors of monoacylglycerol lipase and methods of their use
WO2013056096A1 (en) 2011-10-13 2013-04-18 Angiochem Inc. Polypeptide-opioid conjugates and uses thereof
PE20150041A1 (es) 2011-10-27 2015-01-28 Massachusetts Inst Technology Derivados de aminoacidos funcionalizados en la terminal n capaces de formar microesferas encapsuladoras de farmaco
US9403820B2 (en) 2011-11-11 2016-08-02 Intellikine Llc Kinase inhibitor polymorphs
CA2857548A1 (en) 2011-12-01 2013-06-06 Angiochem Inc. Targeted enzyme compounds and uses thereof
AU2012344702A1 (en) 2011-12-01 2014-06-19 Angiochem Inc. Targeted lysosomal enzyme compounds
ES2843402T3 (es) 2011-12-13 2021-07-16 Engeneic Molecular Delivery Pty Ltd Minicélulas intactas de origen bacteriano para la administración de agentes terapéuticos a tumores cerebrales
CN104245794A (zh) 2011-12-16 2014-12-24 麻省理工学院 α-氨基脒聚合物及其用途
WO2013120107A1 (en) 2012-02-09 2013-08-15 University Of Rochester Methods and compositions for treating a subject to inhibit hearing loss
US20150037281A1 (en) 2012-03-02 2015-02-05 Icahn School Of Medicine At Mount Sinai Variants of prothymosin alpha and methods of using same
CA3152081A1 (en) 2012-04-04 2013-10-10 Halozyme, Inc. Combination therapy with an anti-hyaluronan agent and a tumor-targeted taxane
WO2013162757A1 (en) 2012-04-26 2013-10-31 Yale University Cytotoxic-drug delivering molecules targeting hiv (cdm-hs), cytotoxic activity against the human immunodeficiency virus and methods of use
WO2013185235A1 (en) 2012-06-15 2013-12-19 Angiochem Inc. Targeted iduronidase compounds

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