WO2008010984A3 - Acridine activation of p53 and uses thereof - Google Patents

Acridine activation of p53 and uses thereof Download PDF

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Publication number
WO2008010984A3
WO2008010984A3 PCT/US2007/016122 US2007016122W WO2008010984A3 WO 2008010984 A3 WO2008010984 A3 WO 2008010984A3 US 2007016122 W US2007016122 W US 2007016122W WO 2008010984 A3 WO2008010984 A3 WO 2008010984A3
Authority
WO
WIPO (PCT)
Prior art keywords
acridine
activation
apoptosis
stabilization
cancer
Prior art date
Application number
PCT/US2007/016122
Other languages
French (fr)
Other versions
WO2008010984A2 (en
WO2008010984A9 (en
Inventor
Wafik S El-Deiry
Original Assignee
Univ Pennsylvania
Wafik S El-Deiry
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 Univ Pennsylvania, Wafik S El-Deiry filed Critical Univ Pennsylvania
Publication of WO2008010984A2 publication Critical patent/WO2008010984A2/en
Publication of WO2008010984A9 publication Critical patent/WO2008010984A9/en
Publication of WO2008010984A3 publication Critical patent/WO2008010984A3/en

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C07D219/10—Nitrogen atoms attached in position 9
    • C07D219/12—Amino-alkylamino radicals attached in position 9
    • 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
    • A61K9/0012—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

Abstract

This invention relates to the stabilization of p53 in cells, thereby inducing eitrher cell cycle arrest or apoptosis or both and the consequence of such stabilization on the treatment of cancer. Specifically, the use of acridine and its derivatives in stabilizing p53 through blockage of its ubiquitation, thereby inducing cell cycle arrest or apoptosis in a cell; and the use of these compounds in the treatment of cancer.
PCT/US2007/016122 2006-07-17 2007-07-16 Acridine activation of p53 and uses thereof WO2008010984A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US83120106P 2006-07-17 2006-07-17
US60/831,201 2006-07-17

Publications (3)

Publication Number Publication Date
WO2008010984A2 WO2008010984A2 (en) 2008-01-24
WO2008010984A9 WO2008010984A9 (en) 2008-03-06
WO2008010984A3 true WO2008010984A3 (en) 2008-08-14

Family

ID=38957302

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/016122 WO2008010984A2 (en) 2006-07-17 2007-07-16 Acridine activation of p53 and uses thereof

Country Status (1)

Country Link
WO (1) WO2008010984A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011046757A2 (en) 2009-10-12 2011-04-21 Rajabrata Sarkar Accelerating thrombus resolution through augmentation of p53 activity
MX2012006580A (en) * 2009-12-11 2012-09-28 Genecode As Methods of facilitating neural cell survival using gdnf family ligand (gfl) mimetics or ret signaling pathway activators.
US20130102627A1 (en) * 2010-04-09 2013-04-25 The Brigham And Women's Hospital, Inc. Acridines As Inhibitors Of Haspin And DYRK Kinases
WO2015153535A1 (en) * 2014-03-31 2015-10-08 MiRx Pharmaceuticals, LLC Novel hdmx inhibitors and their use for cancer treatment

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BOYD M. ET AL.: "NMR Studies of Configuration and Tautomeric Equilibria in Nitroacridine Antitumor Agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 33, no. 9, September 1990 (1990-09-01), pages 2656 - 2659 *
WANG W. ET AL.: "Acridine Derivatives Activate p53 and Induce Tumor Cell Death through Bax", CANCER BIOLOGY & THERAPY, vol. 5, no. 8, August 2005 (2005-08-01), pages 893 - 898 *

Also Published As

Publication number Publication date
WO2008010984A2 (en) 2008-01-24
WO2008010984A9 (en) 2008-03-06

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