WO2008106507A3 - Mdm2/mdmx inhibitor peptide - Google Patents

Mdm2/mdmx inhibitor peptide Download PDF

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Publication number
WO2008106507A3
WO2008106507A3 PCT/US2008/055116 US2008055116W WO2008106507A3 WO 2008106507 A3 WO2008106507 A3 WO 2008106507A3 US 2008055116 W US2008055116 W US 2008055116W WO 2008106507 A3 WO2008106507 A3 WO 2008106507A3
Authority
WO
WIPO (PCT)
Prior art keywords
mdm2
mdmx
dual
inhibitory
apoptosis
Prior art date
Application number
PCT/US2008/055116
Other languages
French (fr)
Other versions
WO2008106507A2 (en
Inventor
Jiandong Chen
Baoli Hu
Original Assignee
Univ South Florida
Jiandong Chen
Baoli Hu
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 South Florida, Jiandong Chen, Baoli Hu filed Critical Univ South Florida
Publication of WO2008106507A2 publication Critical patent/WO2008106507A2/en
Publication of WO2008106507A3 publication Critical patent/WO2008106507A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4747—Apoptosis related proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention relates to the use of dual inhibitor of p53 regulatory proteins to selectively inhibit neoplastic growth and induce apoptosis in unregulated cells. A novel peptide that inhibits p53 interactions with MDM2 and MDMX was identified and inserted into a virus nucleic acid sequence to serve as a cell-permeable activator of the p53 tumor suppressor protein. The invention also provides a method of treating cancer by administering a dual-specific inhibitor MDM2/MDMX inhibitory protein into p53+ cancer cells. Administration of the MDM2/MDMX-inhibitory adenovirus is shown to induce cell cycle arrest and apoptosis in a p53-dependent manner.
PCT/US2008/055116 2007-02-27 2008-02-27 Mdm2/mdmx inhibitor peptide WO2008106507A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US89182907P 2007-02-27 2007-02-27
US60/891,829 2007-02-27

Publications (2)

Publication Number Publication Date
WO2008106507A2 WO2008106507A2 (en) 2008-09-04
WO2008106507A3 true WO2008106507A3 (en) 2008-11-06

Family

ID=39721830

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/055116 WO2008106507A2 (en) 2007-02-27 2008-02-27 Mdm2/mdmx inhibitor peptide

Country Status (1)

Country Link
WO (1) WO2008106507A2 (en)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5649825B2 (en) 2007-01-31 2015-01-07 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド Stabilized p53 peptides and methods of use thereof
ES2430067T3 (en) 2007-03-28 2013-11-18 President And Fellows Of Harvard College Sewn polypeptides
US8343760B2 (en) * 2008-06-05 2013-01-01 University Of Maryland, Baltimore p53 activator peptides
KR20120099462A (en) 2009-11-12 2012-09-10 더 리젠츠 오브 더 유니버시티 오브 미시건 Spiro-oxindole mdm2 antagonists
KR20170058446A (en) 2010-08-13 2017-05-26 에일러론 테라퓨틱스 인코포레이티드 Peptidomimetic macrocycles
SG190230A1 (en) 2010-11-12 2013-06-28 Univ Michigan Spiro-oxindole mdm2 antagonists
JP2014502152A (en) * 2010-11-12 2014-01-30 ダナ ファーバー キャンサー インスティテュート，インコーポレイテッド Cancer treatment and diagnosis
WO2012135149A2 (en) * 2011-03-25 2012-10-04 Indiana University Research And Technology Corporation Small molecule modulators of sirt1 activity activate p53 and suppress tumor growth
SG194873A1 (en) 2011-05-11 2013-12-30 Sanofi Sa Spiro-oxindole mdm2 antagonists
RU2639523C2 (en) 2011-10-18 2017-12-21 Эйлерон Терапьютикс, Инк. Peptidomimetic macrocycles and their application
SG11201402131TA (en) * 2011-11-09 2014-08-28 Merz Pharma Gmbh & Co Kgaa Neurotoxins exhibiting shortened biological activity
CA2862038C (en) 2012-02-15 2021-05-25 Aileron Therapeutics, Inc. Peptidomimetic macrocycles
CA2864120A1 (en) 2012-02-15 2013-08-22 Aileron Therapeutics, Inc. Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles
ITRM20120060A1 (en) 2012-02-21 2013-08-22 Consiglio Nazionale Ricerche PEPTIDES ABLE TO RELEASE THE MDM2 / MDM4 HETERODYMER AND THEIR USE IN CANCER TREATMENT.
JP6526563B2 (en) 2012-11-01 2019-06-05 エイルロン セラピューティクス，インコーポレイテッド Disubstituted amino acids and methods for their preparation and use
KR102092345B1 (en) 2013-09-30 2020-03-24 삼성전자주식회사 Leucine zipper variant and use thereof
WO2015116735A1 (en) 2014-01-28 2015-08-06 Mayo Foundation For Medical Education And Research Methods and combinations for killing senescent cells and for treating senescence-associated diseases and disorders
AU2015211021B2 (en) 2014-01-28 2020-07-02 Buck Institute For Research On Aging Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
CA2961029A1 (en) 2014-09-24 2016-03-31 Aileron Therapeutics, Inc. Peptidomimetic macrocycles and formulations thereof
MX2017003797A (en) 2014-09-24 2017-06-15 Aileron Therapeutics Inc Peptidomimetic macrocycles and uses thereof.
CN107614003A (en) 2015-03-20 2018-01-19 艾瑞朗医疗公司 Peptidomimetic macrocyclic compound and application thereof
KR20160126340A (en) 2015-04-23 2016-11-02 삼성전자주식회사 Three-helix bundle protein and use thereof
US10023613B2 (en) 2015-09-10 2018-07-17 Aileron Therapeutics, Inc. Peptidomimetic macrocycles as modulators of MCL-1
SG11201808728QA (en) 2016-04-06 2018-11-29 Univ Michigan Regents Mdm2 protein degraders
US10759808B2 (en) 2016-04-06 2020-09-01 The Regents Of The University Of Michigan Monofunctional intermediates for ligand-dependent target protein degradation
PL3458101T3 (en) 2016-05-20 2021-05-31 F. Hoffmann-La Roche Ag Protac antibody conjugates and methods of use
WO2019133179A2 (en) * 2017-12-01 2019-07-04 Massachusetts Institute Of Technology Solution-phase affinity selection of inhibitors from combinatorial peptide libraries
WO2020023502A1 (en) 2018-07-23 2020-01-30 Aileron Therapeutics, Inc. Peptidomimetic macrocycles and uses thereof
CN110256551A (en) * 2019-03-13 2019-09-20 中山大学附属第五医院 The polypeptide of specific bond DDX24 unwindase and its application
WO2022081827A1 (en) 2020-10-14 2022-04-21 Dana-Farber Cancer Institute, Inc. Chimeric conjugates for degradation of viral and host proteins and methods of use
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHENE P.: "Inhibition of the p53-MDM2 interaction: targeting a protein-protein interface", MOLECULAR CANCER RESEARCH, vol. 2, January 2004 (2004-01-01), pages 20 - 28 *
HU B. ET AL.: "MDMX overexpression prevents p53 activation by the MDM2 inhibitor nutlin", vol. 281, no. 44, 3 November 2006 (2006-11-03), pages 33030 - 33035, XP055139882, DOI: doi:10.1074/jbc.C600147200 *

Also Published As

Publication number Publication date
WO2008106507A2 (en) 2008-09-04

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