WO2017136731A1 - Rapaglutins, novel inhibitors of glut and use thereof - Google Patents

Rapaglutins, novel inhibitors of glut and use thereof Download PDF

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Publication number
WO2017136731A1
WO2017136731A1 PCT/US2017/016516 US2017016516W WO2017136731A1 WO 2017136731 A1 WO2017136731 A1 WO 2017136731A1 US 2017016516 W US2017016516 W US 2017016516W WO 2017136731 A1 WO2017136731 A1 WO 2017136731A1
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cancer
disease
syndrome
autoimmune
compound
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PCT/US2017/016516
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English (en)
French (fr)
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WO2017136731A8 (en
Inventor
Liu Jun
Jingxin Wang
Guo ZUFENG
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Johns Hopkins University
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Johns Hopkins University
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Priority to AU2017213630A priority Critical patent/AU2017213630B2/en
Priority to US16/074,300 priority patent/US11708391B2/en
Priority to MX2018009408A priority patent/MX2018009408A/es
Priority to JP2018540115A priority patent/JP7104627B2/ja
Priority to EP17748278.3A priority patent/EP3411046B1/en
Priority to CA3013783A priority patent/CA3013783A1/en
Priority to CN201780010180.3A priority patent/CN108697729B/zh
Publication of WO2017136731A1 publication Critical patent/WO2017136731A1/en
Anticipated expiration legal-status Critical
Publication of WO2017136731A8 publication Critical patent/WO2017136731A8/en
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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
    • A61K31/12—Ketones
    • 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
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
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    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
    • C—CHEMISTRY; METALLURGY
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    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
    • C07K5/126—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • Glucose is the main source of energy in eukaryotic organisms and plays a central role in metabolism and cellular homeostasis.
  • Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because tumors are fast growing, they need the proteins that carry nutrients into the cells to function at full capacity. Therefore, an important strategy for cancer treatment would be to block these proteins. Since the GLUT family is one of the major group of membrane transport proteins that transport glucose and other substances into cells, inhibiting these proteins should be important in stopping the spread of cancer. In addition, GLUT also plays a key role in T lymphocyte activation. Inhibition of glucose transport can modulate immune response and have implication in the treatment of a wide variety of immune related diseases from graft rejection to various autoimmune diseases.
  • Figures 28A-28D (a) A18 and El l inhibit FAT and A18, but not El l, stimulates SRE reporter gene signal, (b) El 1 inhibits NFAT, NF- ⁇ and IL2, but not MEF-2 or AP-1 pathways, in Jurkat T cells, (c) Glucose inhibitor stimulates SRE reporter gene signal, (d) Glucose inhibitors inhibit F AT reporter gene signal.
  • chemotherapeutic agents can be used prior to, simultaneously with or following treatment with invention compounds.
  • Illustrative agents include but are not limited to, taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof.
  • Therapeutic antibodies or other proteins are also envisioned in combination therapies of the invention.
  • a 45,000 compound and 3000 pool rapafucin library were screened using the alamar blue cell viability assay with the human non-small cell lung cancer (NSCLC) cell line A549.
  • NSCLC human non-small cell lung cancer

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
PCT/US2017/016516 2016-02-04 2017-02-03 Rapaglutins, novel inhibitors of glut and use thereof Ceased WO2017136731A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
AU2017213630A AU2017213630B2 (en) 2016-02-04 2017-02-03 Rapaglutins, novel inhibitors of GLUT and use thereof
US16/074,300 US11708391B2 (en) 2016-02-04 2017-02-03 Rapaglutins, novel inhibitors of GLUT and use thereof
MX2018009408A MX2018009408A (es) 2016-02-04 2017-02-03 Rapaglutinas, nuevos inhibidores de transportadores de glucosa (glut) y uso de los mismos.
JP2018540115A JP7104627B2 (ja) 2016-02-04 2017-02-03 ラパグルチン（ｒａｐａｇｌｕｔｉｎｓ）、ｇｌｕｔの新規阻害剤及びその使用
EP17748278.3A EP3411046B1 (en) 2016-02-04 2017-02-03 Rapaglutins, novel inhibitors of glut and use thereof
CA3013783A CA3013783A1 (en) 2016-02-04 2017-02-03 Rapaglutins, novel inhibitors of glut and use thereof
CN201780010180.3A CN108697729B (zh) 2016-02-04 2017-02-03 新型GLUT抑制剂rapaglutin及其用途

Applications Claiming Priority (2)

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US201662291453P 2016-02-04 2016-02-04
US62/291,453 2016-02-04

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WO2017136731A8 WO2017136731A8 (en) 2018-08-23

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US (1) US11708391B2 (enExample)
EP (1) EP3411046B1 (enExample)
JP (1) JP7104627B2 (enExample)
CN (1) CN108697729B (enExample)
AU (1) AU2017213630B2 (enExample)
CA (1) CA3013783A1 (enExample)
MX (1) MX2018009408A (enExample)
WO (1) WO2017136731A1 (enExample)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3411032A4 (en) * 2016-02-04 2019-08-14 The Johns Hopkins University RAPADOCINES, INHIBITORS OF THE EQUILIBRATION NUCLEOSIDE TRANSPORTER 1 AND USES THEREOF
WO2021067439A1 (en) 2019-10-01 2021-04-08 The Johns Hopkins University Rapafucin derivative compounds and methods of use thereof
US11066416B2 (en) 2016-02-04 2021-07-20 The Johns Hopkins University Rapafucin derivative compounds and methods of use thereof
US11708391B2 (en) 2016-02-04 2023-07-25 The Johns Hopkins University Rapaglutins, novel inhibitors of GLUT and use thereof

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021067405A1 (en) * 2019-10-01 2021-04-08 The Johns Hopkins University Neuroprotective compounds and methods of use thereof
CN112294792B (zh) * 2020-09-22 2021-10-22 厦门市中医院 化合物wzb117在制备治疗和/或预防肝损伤药物中的用途
CN115364224B (zh) * 2022-08-25 2024-02-02 杭州天玑济世生物科技有限公司 Glut1抑制剂作为线粒体自噬诱导剂的用途
CN120271673A (zh) * 2024-01-08 2025-07-08 重庆医科大学 一种化合物、包含其的药物组合物及其用途
CN120617307B (zh) * 2025-06-16 2025-12-09 烟台大学 一种wzb117纳米制剂及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140073581A1 (en) 2010-11-30 2014-03-13 The Johns Hopkins University Hybrid Cyclic Libraries and Screens Thereof
US20140206624A1 (en) * 2011-02-04 2014-07-24 The Brigham And Women's Hospital, Inc. Treatment of leukemia
US20150050356A1 (en) 2007-03-07 2015-02-19 Abraxis Bioscience, Llc Nanoparticle comprising rapamycin and albumin as anticancer agent

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5100899A (en) 1989-06-06 1992-03-31 Roy Calne Methods of inhibiting transplant rejection in mammals using rapamycin and derivatives and prodrugs thereof
US5457194A (en) 1993-03-17 1995-10-10 Abbott Laboratories Substituted aliphatic amine-containing macrocyclic immunomodulators
US5798355A (en) 1995-06-07 1998-08-25 Gpi Nil Holdings, Inc. Inhibitors of rotamase enzyme activity
US5527907A (en) 1993-11-19 1996-06-18 Abbott Laboratories Macrolide immunomodulators
US7056935B2 (en) 1995-06-07 2006-06-06 Gpi Nil Holdings, Inc. Rotamase enzyme activity inhibitors
US5696135A (en) 1995-06-07 1997-12-09 Gpi Nil Holdings, Inc. Inhibitors of rotamase enzyme activity effective at stimulating neuronal growth
US6984635B1 (en) 1998-02-13 2006-01-10 Board Of Trustees Of The Leland Stanford Jr. University Dimerizing agents, their production and use
EP1352910A1 (en) 2002-04-10 2003-10-15 Grünenthal GmbH New analogs of nitrobenzylthioinosine
EP2143727B1 (en) 2003-04-18 2015-01-21 Enanta Pharmaceuticals, Inc. Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors
WO2005117562A2 (en) 2004-06-04 2005-12-15 Xenoport, Inc. Ent1 transporters expressed in cancer cells
GB0417852D0 (en) 2004-08-11 2004-09-15 Biotica Tech Ltd Production of polyketides and other natural products
CA2626325A1 (en) 2005-10-28 2007-05-10 Praecis Pharmaceuticals Incorporated Methods for identifying compounds of interest using encoded libraries
US20080306098A1 (en) 2006-11-06 2008-12-11 Mutz Mitchell W Pharmacokinetics of protease inhibitors and other drugs
CA2688240A1 (en) 2007-05-24 2008-12-04 The United States Government As Represented By The Department Of Veterans Affairs Intranuclear protein transduction through a nucleoside salvage pathway
JP2011524413A (ja) 2008-06-17 2011-09-01 バイオチカ テクノロジー リミテッド 新規化合物、及びこれらの製造のための方法
EP2607352A1 (en) 2011-12-22 2013-06-26 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Pipecolate-diketoamides for treatment of psychiatric disorders
KR101733736B1 (ko) 2012-01-06 2017-05-10 삼성에스디아이 주식회사 리튬 이차 전지용 음극 활물질, 그 제조 방법 및 이를 포함하는 리튬 이차 전지
WO2014008636A1 (en) 2012-07-11 2014-01-16 Merck Sharp & Dohme Corp. Macrocyclic compounds as hiv integrase inhibitors
US10167259B2 (en) 2013-06-14 2019-01-01 The Board Of Regents Of The University Of Texas System Allosteric inhibitors of proteasome and methods of use thereof
WO2016112295A1 (en) 2015-01-09 2016-07-14 Warp Drive Bio, Inc. Compounds that participate in cooperative binding and uses thereof
EP3355930A4 (en) 2015-10-01 2019-03-06 Warp Drive Bio, Inc. METHOD AND REAGENTS FOR THE ANALYSIS OF PROTEIN-PROTEIN INTERFACES
US11066416B2 (en) 2016-02-04 2021-07-20 The Johns Hopkins University Rapafucin derivative compounds and methods of use thereof
US10662220B2 (en) * 2016-02-04 2020-05-26 The Johns Hopkins University Synthesis and composition of rapafucin libraries
MX380313B (es) * 2016-02-04 2025-03-12 Univ Johns Hopkins Rapadocinas, inhibidores de transportador 1 de nucleósido equilibrador y usos de los mismos.
MX2018009408A (es) 2016-02-04 2018-11-09 Univ Johns Hopkins Rapaglutinas, nuevos inhibidores de transportadores de glucosa (glut) y uso de los mismos.
MX386103B (es) 2016-04-22 2025-03-18 Astrazeneca Ab Inhibidores de mcl-1 y metodos de uso de los mismos.
CA3035757A1 (en) 2016-09-02 2018-03-08 The Johns Hopkins University Mif inhibitors and methods of use thereof
UY37900A (es) 2017-09-26 2019-04-30 Novartis Ag Nuevos derivados de rapamicina

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150050356A1 (en) 2007-03-07 2015-02-19 Abraxis Bioscience, Llc Nanoparticle comprising rapamycin and albumin as anticancer agent
US20140073581A1 (en) 2010-11-30 2014-03-13 The Johns Hopkins University Hybrid Cyclic Libraries and Screens Thereof
US20140206624A1 (en) * 2011-02-04 2014-07-24 The Brigham And Women's Hospital, Inc. Treatment of leukemia

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3411046A4

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3411032A4 (en) * 2016-02-04 2019-08-14 The Johns Hopkins University RAPADOCINES, INHIBITORS OF THE EQUILIBRATION NUCLEOSIDE TRANSPORTER 1 AND USES THEREOF
US10774110B2 (en) 2016-02-04 2020-09-15 The Johns Hopkins University Rapadocins, inhibitors of equilibrative nucleoside transporter 1 and uses thereof
EP3782636A1 (en) * 2016-02-04 2021-02-24 The Johns Hopkins University Rapadocins, inhibitors of equilibrative nucleoside transporter 1 and uses thereof
US11066416B2 (en) 2016-02-04 2021-07-20 The Johns Hopkins University Rapafucin derivative compounds and methods of use thereof
US11555054B2 (en) 2016-02-04 2023-01-17 The Johns Hopkins University Rapadocins, inhibitors of equilibrative nucleoside transporter 1 and uses thereof
US11708391B2 (en) 2016-02-04 2023-07-25 The Johns Hopkins University Rapaglutins, novel inhibitors of GLUT and use thereof
US11945827B2 (en) 2016-02-04 2024-04-02 The Johns Hopkins University Rapafucin derivative compounds and methods of use thereof
WO2021067439A1 (en) 2019-10-01 2021-04-08 The Johns Hopkins University Rapafucin derivative compounds and methods of use thereof
EP4037702A4 (en) * 2019-10-01 2023-10-18 The Johns Hopkins University Rapafucin derivative compounds and methods of use thereof

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US20210214390A1 (en) 2021-07-15
JP7104627B2 (ja) 2022-07-21
EP3411046B1 (en) 2025-07-16
MX2018009408A (es) 2018-11-09
WO2017136731A8 (en) 2018-08-23
EP3411046A4 (en) 2019-11-27
EP3411046A1 (en) 2018-12-12
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