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WO2008110491A3 - Chemotherapy of neoplastic diseases using combinations of rapamycin and compounds modulating mtor pathway alone or in combination with heat - Google Patents

Chemotherapy of neoplastic diseases using combinations of rapamycin and compounds modulating mtor pathway alone or in combination with heat Download PDF

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Publication number
WO2008110491A3
WO2008110491A3 PCT/EP2008/052682 EP2008052682W WO2008110491A3 WO 2008110491 A3 WO2008110491 A3 WO 2008110491A3 EP 2008052682 W EP2008052682 W EP 2008052682W WO 2008110491 A3 WO2008110491 A3 WO 2008110491A3
Authority
WO
WIPO (PCT)
Prior art keywords
rapamycin
combination
mtor pathway
neoplastic diseases
chemotherapy
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.)
Ceased
Application number
PCT/EP2008/052682
Other languages
French (fr)
Other versions
WO2008110491A2 (en
Inventor
Christoph Moroni
Don Benjamin
Marco Colombi
Klaus-Dieter Molle
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Universitaet Basel
Original Assignee
Universitaet Basel
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Universitaet Basel filed Critical Universitaet Basel
Publication of WO2008110491A2 publication Critical patent/WO2008110491A2/en
Publication of WO2008110491A3 publication Critical patent/WO2008110491A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/155Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (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)

Abstract

The invention relates to compounds blocking or activating the mTOR pathway for use as a medicament in combination with rapamycin or a rapamycin-like compound and/or with metformin or a metformin-like compound and/or with thermal energy, for the treatment of neoplastic diseases, hyperproliferative conditions or other processes wherein mTOR is implicated. Experiments are described which demonstrate that mutational loss of Tsc2 or PTEN or down-regulating Tsc2 or PTEN by shRNA sensitizes cells for rapamycin and metformin and for thermal treatment, with synergies of these three forms of treatments. The invention further relates to a method to predict sensitivity of a tumor to the combination of mTOR pathway inhibition combined with application of thermal energy.
PCT/EP2008/052682 2007-03-09 2008-03-05 Chemotherapy of neoplastic diseases using combinations of rapamycin and compounds modulating mtor pathway alone or in combination with heat Ceased WO2008110491A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP07103873 2007-03-09
EP07103873.1 2007-03-09

Publications (2)

Publication Number Publication Date
WO2008110491A2 WO2008110491A2 (en) 2008-09-18
WO2008110491A3 true WO2008110491A3 (en) 2008-12-11

Family

ID=39760141

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/052682 Ceased WO2008110491A2 (en) 2007-03-09 2008-03-05 Chemotherapy of neoplastic diseases using combinations of rapamycin and compounds modulating mtor pathway alone or in combination with heat

Country Status (1)

Country Link
WO (1) WO2008110491A2 (en)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009112266A1 (en) * 2008-03-12 2009-09-17 Ludwig-Maximilians-Universität Active substance combination with gemcitabine for the treatment of epithelial cancer
WO2010022243A1 (en) * 2008-08-20 2010-02-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chemoprevention of head and neck squamous cell carcinomas
KR20120080579A (en) * 2009-08-25 2012-07-17 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 Use of metformin in cancer treatment and prevention
US20140235558A1 (en) * 2010-06-15 2014-08-21 Hanall Biopharma Co., Ltd. Pharmaceutical composition having activity of anticancer
CA2824096A1 (en) * 2011-01-11 2012-07-19 Universitat Basel Combination of syrosingopine and mitochondrial inhibitors for the treatment of cancer and immunosuppression
GB201120779D0 (en) 2011-12-02 2012-01-11 Immodulon Therapeutics Ltd Cancer therapy
WO2013086002A1 (en) * 2011-12-05 2013-06-13 Cellworks Research India Private Limited Compositions, process of preparation of said compositions and method of treating cancer
GB201308325D0 (en) * 2013-05-09 2013-06-19 Immodulon Therapeutics Ltd Cancer Therapy
GB201322725D0 (en) 2013-12-20 2014-02-05 Immodulon Therapeutics Ltd Cancer therapy
WO2016014530A1 (en) 2014-07-21 2016-01-28 Novartis Ag Combinations of low, immune enhancing. doses of mtor inhibitors and cars
US11542488B2 (en) 2014-07-21 2023-01-03 Novartis Ag Sortase synthesized chimeric antigen receptors
WO2016014565A2 (en) 2014-07-21 2016-01-28 Novartis Ag Treatment of cancer using humanized anti-bcma chimeric antigen receptor
CN107109420A (en) 2014-07-21 2017-08-29 诺华股份有限公司 Cancer Therapy Using CLL-1 Chimeric Antigen Receptor
CA2990107A1 (en) 2015-06-24 2016-12-29 Immodulon Therapeutics Limited A checkpoint inhibitor and a whole cell mycobacterium for use in cancer therapy
KR101832892B1 (en) * 2015-08-24 2018-02-27 가톨릭대학교 산학협력단 Metformin-comprising compositions for preventing or treating mitochondrial diseases caused by immunosuppressive drugs and immune diseases
US10683308B2 (en) 2015-09-11 2020-06-16 Navitor Pharmaceuticals, Inc. Rapamycin analogs and uses thereof
US10765665B2 (en) * 2015-11-24 2020-09-08 Melin Jeffrey Composition comprising combination of rapamycin and an activator of AMP kinase and use thereof for treating diseases
WO2019118407A1 (en) * 2017-12-11 2019-06-20 The Jackson Laboratory Combination therapies for treatment of type ii diabetes
CN117887659A (en) * 2018-05-01 2024-04-16 云南济慈再生医学研究院有限公司 A method for promoting differentiation of target cells into neural cells
WO2019241426A1 (en) 2018-06-13 2019-12-19 Novartis Ag Bcma chimeric antigen receptors and uses thereof
CN112423843B (en) 2018-06-15 2023-11-28 詹森药业有限公司 Rapamycin analogues and uses thereof
WO2021113665A1 (en) 2019-12-05 2021-06-10 Navitor Pharmaceuticals, Inc. Rapamycin analogs and uses thereof
CN114621338B (en) * 2022-03-11 2022-11-11 中山大学 mTOR inhibitor and application thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DEGRAFFENRIED L A ET AL: "Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway.", ANNALS OF ONCOLOGY : OFFICIAL JOURNAL OF THE EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY / ESMO OCT 2004, vol. 15, no. 10, October 2004 (2004-10-01), pages 1510 - 1516, XP002497599, ISSN: 0923-7534 *
IWAMARU A ET AL: "Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells", ONCOGENE, vol. 26, no. 13, 25 September 2006 (2006-09-25), pages 1840 - 1851, XP002497598, ISSN: 0950-9232 *
WUST P ET AL: "Hyperthermia in combined treatment of cancer", LANCET ONCOLOGY, LANCET PUBLISHING GROUP, LONDON, GB, vol. 3, no. 8, 1 August 2002 (2002-08-01), pages 487 - 497, XP004813895, ISSN: 1470-2045 *
ZAKIKHANI MAHVASH ET AL: "Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells", CANCER RESEARCH, vol. 66, no. 21, November 2006 (2006-11-01), pages 10269 - 10273, XP002497600, ISSN: 0008-5472 *

Also Published As

Publication number Publication date
WO2008110491A2 (en) 2008-09-18

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