EP0877608A1 - SENSIBILISATION AUX SUBSTANCES CHIMIOTHERAPEUTIQUES DES CELLULES CANCEREUSES SUREXPRIMANT HER2/neu - Google Patents

SENSIBILISATION AUX SUBSTANCES CHIMIOTHERAPEUTIQUES DES CELLULES CANCEREUSES SUREXPRIMANT HER2/neu

Info

Publication number
EP0877608A1
EP0877608A1 EP97904188A EP97904188A EP0877608A1 EP 0877608 A1 EP0877608 A1 EP 0877608A1 EP 97904188 A EP97904188 A EP 97904188A EP 97904188 A EP97904188 A EP 97904188A EP 0877608 A1 EP0877608 A1 EP 0877608A1
Authority
EP
European Patent Office
Prior art keywords
emodin
tyrosine kinase
cells
cell
kinase inhibitor
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.)
Withdrawn
Application number
EP97904188A
Other languages
German (de)
English (en)
Inventor
Mien-Chie Hung
Lisha Zhang
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.)
University of Texas System
Original Assignee
University of Texas System
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 University of Texas System filed Critical University of Texas System
Publication of EP0877608A1 publication Critical patent/EP0877608A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • Lung cancers are usually divided into two groups by clinical and biological criteria: (1 ) non-small-cell lung cancer (NSCLC) (Boring et aL. 1994). and (2 ) small-cell lung cancer (SCLC).
  • NSCLC non-small-cell lung cancer
  • SCLC small-cell lung cancer
  • Most small-cell lung cancers are sensitive to chemotherapy, whereas NSCLC usually are refractory to chemotherapy at the time of diagnosis (Minna et ai, 1989). Thus NSCLC are the cause of most lung cancer deaths (Boring, et ai. 1994).
  • intensive effort has been made to characterize specific gene alteration in lung cancers and to develop therapies that target those genes.
  • neu oncogenes are associated with the proliferative potential.
  • new-mediated cancers appear to be resistant to host defense mechanisms.
  • overexpression of the neu oncogene in transfected cells results in resistance to tumor necrosis factor, a major effector molecule in macrophage-mediated tumor cell cytotoxicity.
  • neu expression has also been detected in ovarian cancer and its overexpression results in poor prognosis.
  • the expression of neu oncogenes in human tumor cells induce resistance to several host cytotoxic mechanisms.
  • second agents that may be used with emodin or emodin-like tyrosine kinase inhibitor are anti-neoplastic agents.
  • examples of these are cisplatin; doxorubicin (Mechetner & Roninson, 1992) and analogues, such as 14-O-hemiesters of doxorubicin; etoposide; vincristine (Shirai et al., 1994; Friche et aL, 1993); vinblastine (Bear, 1994; McKinney & Hosford, 1993); actinomycin D (McKinney & Hosford, 1993); daunomycin (Bear, 1994); daunorubicin (Muller et al., 1994); taxotere (Hunter et al., 1993); taxol (Mechetner & Roninson, 1992); and tamoxifen (Trump et al.. 1992).
  • the skilled artisan is directed to "Phy
  • Agents that directly cross-link nucleic acids, specifically DNA, are envisaged and are shown herein, to eventuate DNA damage leading to a synergistic antineoplastic combination Agents such as cisplatin. and other DNA alkvlating agents may be used.
  • emodin as an exemplary emodm-like inhibitor to synergistically enhance the antineoplastic effects of the doxorubicin in the treatment of cancers.
  • Those of skill in the art will be able to use the invention as exemplified potentiate the effects of doxorubicin in a range of different new-mediated cancers.
  • Vincristine has been effective in Hodgkin's disease and other lymphomas. Although it appears to be somewhat less beneficial than vinblastine when used alone in Hodgkin's disease, when used with mechlorethamine, prednisone. and procarbazme (the so-called MOPP regimen), it is the preferred treatment for the advanced stages (DI and IV) of this disease. In non-Hodgkin's lymphomas, vincristine is an important agent, particularly when used with cyclophosphamide, bleomycin, doxorubicin. and prednisone. Vincristine is more useful than vinblastine in lymphocytic leukemia.
  • Vinblastine is metabolized in the liver to biologically activate denvative desacetylvinblasune Approximately 15% of an administered dose is detected intact in the u ⁇ ne, and about 10% is recovered in the feces after biliary excretion Doses should be reduced in patients with hepatic dysfunction At least a 50% reduction in dosage is indicated if the concentration of bilirubm m plasma is greater than 3 mg dl (about 50 mM).
  • the active compounds of the present invention will often be formulated for parenteral administration, e g , formulated for injection via the intravenous, intramuscular, sub-cutaneous, or even intraperitoneal routes
  • parenteral administration e g
  • aqueous composition that contains emodin or emodm-like compounds alone or in combination with a second agent as active ingredients
  • Such compositions can be prepared as mjectables. either as liquid solutions or suspensions, solid forms suitable for using to prepare solutions or suspensions upon the addition of a liquid pnor to injection can also be prepared; and the preparations can also be emulsified.
  • Example 2 The results from Example 2 show that phosphotyrosme level of pl85 ⁇ "' is repressed by emodin. To examine whether this reduction m tyrosine phosphorylation affects the tyrosine kinase activity of pl85 n ' M . the immuno-complex kinase assay was used.

Landscapes

  • 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)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Méthodes d'inhibition du produit génétique du neu oncogène p185neu tyrosine kinase. La surexpression du neu oncogène conduit à la chimiorésistance. Les méthodes présentées reposent sur l'utilisation nouvelle de l'émodine en association avec des substances chimiothérapeutiques servant à traiter le carcinome. En outre, l'émodine renforce les effets antinéoplasiques des agents chimiothérapeutiques, ce qui n'était pas connu. Selon l'invention, l'émodine sensibilise les cellules cancéreuses pour les rendre sensibles aux traitements par les substances chimiothérapeutiques.
EP97904188A 1996-01-31 1997-01-31 SENSIBILISATION AUX SUBSTANCES CHIMIOTHERAPEUTIQUES DES CELLULES CANCEREUSES SUREXPRIMANT HER2/neu Withdrawn EP0877608A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US1087596P 1996-01-31 1996-01-31
US10875 1996-01-31
PCT/US1997/001686 WO1997027848A1 (fr) 1996-01-31 1997-01-31 SENSIBILISATION AUX SUBSTANCES CHIMIOTHERAPEUTIQUES DES CELLULES CANCEREUSES SUREXPRIMANT HER2/neu

Publications (1)

Publication Number Publication Date
EP0877608A1 true EP0877608A1 (fr) 1998-11-18

Family

ID=21747830

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97904188A Withdrawn EP0877608A1 (fr) 1996-01-31 1997-01-31 SENSIBILISATION AUX SUBSTANCES CHIMIOTHERAPEUTIQUES DES CELLULES CANCEREUSES SUREXPRIMANT HER2/neu

Country Status (5)

Country Link
EP (1) EP0877608A1 (fr)
JP (1) JP2000504020A (fr)
AU (1) AU1854597A (fr)
CA (1) CA2245165A1 (fr)
WO (1) WO1997027848A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6326356B1 (en) 1996-10-18 2001-12-04 Board Of Regents, The University Of Texas System Suppression of neu overexpression using a mini-E1A gene
US6267958B1 (en) 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
JP4738592B2 (ja) * 1997-10-31 2011-08-03 アーチ・デヴェロップメント・コーポレイション ５α−還元酵素活性を調節するための方法及び組成物
US6627196B1 (en) 1999-08-27 2003-09-30 Genentech, Inc. Dosages for treatment with anti-ErbB2 antibodies
WO2002087618A1 (fr) * 2001-04-27 2002-11-07 Takeda Chemical Industries, Ltd. Methode de prevention et de traitement du cancer
WO2002087619A1 (fr) * 2001-04-27 2002-11-07 Takeda Chemical Industries, Ltd. Methode de prevention et de traitement du cancer
KR20080096705A (ko) 2006-04-07 2008-10-31 선 텐 피토테크 컴퍼니 리미티드 안트라세네디온 화합물
JPWO2007132784A1 (ja) * 2006-05-15 2009-09-24 国立大学法人 新潟大学 アントラキノン誘導体を有効成分として含有する抗精神病薬、認知異常の治療薬
MX2010012501A (es) * 2008-05-16 2010-12-20 Pharma Mar Sa Terapia de combinacion con un alcaloide antitumoral.
US8541382B2 (en) * 2010-11-13 2013-09-24 Sirbal Ltd. Cardiac glycoside analogs in combination with emodin for cancer therapy
RU2693004C1 (ru) * 2019-03-15 2019-07-01 Лейсан Фаридовна Минигулова Противоопухолевая композиция цисплатина с ингибитором 6-фосфоглюконатдегидрогеназы

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4966918A (en) * 1989-01-27 1990-10-30 Sloan-Kettering Institute For Cancer Research Derivatives of chryosphanol
US5436243A (en) * 1993-11-17 1995-07-25 Research Triangle Institute Duke University Aminoanthraquinone derivatives to combat multidrug resistance

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9727848A1 *

Also Published As

Publication number Publication date
CA2245165A1 (fr) 1997-08-07
AU1854597A (en) 1997-08-22
WO1997027848A1 (fr) 1997-08-07
JP2000504020A (ja) 2000-04-04

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