Title:
EIF4A INHIBITORS AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2024/016000
Kind Code:
A3
Abstract:
Described herein, inter alia, are elF4A inhibitors and uses thereof comprising a first elF4A inhibitor attached to a second elF4A inhibitor through a covalent linker. In preferred embodiments, the first elF4A inhibitor and the second elF4A inhibitor are the same and comprise Rocaglamide A, Zotatifin, Silvestrol, Pateamine A or Hippuristanol, and the linker comprises polyethylene glycol, polyethylene imine or polyethylene sulfide. Further provided a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound and a method of treating cancer in a subject in need thereof, said method comprising administering to the subject in need thereof a therapeutically effective amount of a compound.
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Inventors:
SHOKAT KEVAN (US)
LOU KEVIN (US)
MOORE MEGAN (US)
LOU KEVIN (US)
MOORE MEGAN (US)
Application Number:
PCT/US2023/070278
Publication Date:
March 28, 2024
Filing Date:
July 14, 2023
Export Citation:
Assignee:
UNIV CALIFORNIA (US)
International Classes:
A61K31/343; C07D307/83; C07D307/93; C07D405/12
Domestic Patent References:
| WO2020252173A1 | 2020-12-17 |
Other References:
GARIMA AGARWAL, PETER J. BLANCO CARCACHE, ERMIAS MEKURIA ADDO, A. DOUGLAS KINGHORN: "Current status and contemporary approaches to the discovery of antitumor agents from higher plants", BIOTECHNOLOGY ADVANCES, vol. 38, 1 January 2020 (2020-01-01), GB , pages 1 - 27, XP093154785, ISSN: 0734-9750, DOI: 10.1016/j.biotechadv.2019.01.004
WANG DONG; TABTI REDOUANE; ELDERWISH SABRIA; ABOU-HAMDAN HUSSEIN; DJEHAL AMEL; YU PENG; YURUGI HAJIME; RAJALINGAM KRISHNARAJ; NEBI: "Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases", CMLS CELLULAR AND MOLECULAR LIFE SCIENCE, vol. 77, no. 18, 15 February 2020 (2020-02-15), DE , pages 3525 - 3546, XP037228857, ISSN: 1420-682X, DOI: 10.1007/s00018-020-03475-1
FRÉDÉRIC THUAUD; YOHANN BERNARD; GÜLEN TÜRKERI; RONAN DIRR; GENEVIÈVE AUBERT; THIERRY CRESTEIL; AURÉLIE BAGUET; CATHERINE TOMASETT: "Synthetic Analogue of Rocaglaol Displays a Potent and Selective Cytotoxicity in Cancer Cells: Involvement of Apoptosis Inducing Factor and Caspase-12", JOURNAL OF MEDICINAL CHEMISTRY, vol. 52, no. 16, 27 August 2009 (2009-08-27), US , pages 5176 - 5187, XP055561282, ISSN: 0022-2623, DOI: 10.1021/jm900365v
GERNOT POLIER , NEUMANN JENNIFER, THUAUD FRÉDÉRIC, RIBEIRO NIGEL, GELHAUS CHRISTOPH, SCHMIDT HENDRIK, GIAISI MARCO, KÖHLER REBECC: "The Natural Anticancer Compounds Rocaglamides Inhibit the Raf-MEK-ERK Pathway by Targeting Prohibitin 1 and 2", CHEMISTRY & BIOLOGY, vol. 19, no. 9, 21 September 2012 (2012-09-21), GB , pages 1093 - 1104, XP093154818, ISSN: 1074-5521, DOI: 10.1016/j.chembiol.2012.07.012
KEVIN LOU, WASSARMAN DOUGLAS R., YANG TANGPO, PAUNG YITING, ZHANG ZIYANG, O’LOUGHLIN THOMAS A., MOORE MEGAN K., EGAN REGINA K., GR: "IFITM proteins assist cellular uptake of diverse linked chemotypes", SCIENCE, vol. 378, no. 6624, 9 December 2022 (2022-12-09), pages 1097 - 1104, XP093154820, DOI: 10.1126/ science .abl5829
LOU KEVIN: "Investigating therapeutic chemotypes by merging functional genomics and drug design", DISSERTATION, 1 September 2022 (2022-09-01), pages 1 - 158, XP093154830
WANG DONG; TABTI REDOUANE; ELDERWISH SABRIA; ABOU-HAMDAN HUSSEIN; DJEHAL AMEL; YU PENG; YURUGI HAJIME; RAJALINGAM KRISHNARAJ; NEBI: "Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases", CMLS CELLULAR AND MOLECULAR LIFE SCIENCE, vol. 77, no. 18, 15 February 2020 (2020-02-15), DE , pages 3525 - 3546, XP037228857, ISSN: 1420-682X, DOI: 10.1007/s00018-020-03475-1
FRÉDÉRIC THUAUD; YOHANN BERNARD; GÜLEN TÜRKERI; RONAN DIRR; GENEVIÈVE AUBERT; THIERRY CRESTEIL; AURÉLIE BAGUET; CATHERINE TOMASETT: "Synthetic Analogue of Rocaglaol Displays a Potent and Selective Cytotoxicity in Cancer Cells: Involvement of Apoptosis Inducing Factor and Caspase-12", JOURNAL OF MEDICINAL CHEMISTRY, vol. 52, no. 16, 27 August 2009 (2009-08-27), US , pages 5176 - 5187, XP055561282, ISSN: 0022-2623, DOI: 10.1021/jm900365v
GERNOT POLIER , NEUMANN JENNIFER, THUAUD FRÉDÉRIC, RIBEIRO NIGEL, GELHAUS CHRISTOPH, SCHMIDT HENDRIK, GIAISI MARCO, KÖHLER REBECC: "The Natural Anticancer Compounds Rocaglamides Inhibit the Raf-MEK-ERK Pathway by Targeting Prohibitin 1 and 2", CHEMISTRY & BIOLOGY, vol. 19, no. 9, 21 September 2012 (2012-09-21), GB , pages 1093 - 1104, XP093154818, ISSN: 1074-5521, DOI: 10.1016/j.chembiol.2012.07.012
KEVIN LOU, WASSARMAN DOUGLAS R., YANG TANGPO, PAUNG YITING, ZHANG ZIYANG, O’LOUGHLIN THOMAS A., MOORE MEGAN K., EGAN REGINA K., GR: "IFITM proteins assist cellular uptake of diverse linked chemotypes", SCIENCE, vol. 378, no. 6624, 9 December 2022 (2022-12-09), pages 1097 - 1104, XP093154820, DOI: 10.1126/ science .abl5829
LOU KEVIN: "Investigating therapeutic chemotypes by merging functional genomics and drug design", DISSERTATION, 1 September 2022 (2022-09-01), pages 1 - 158, XP093154830
Attorney, Agent or Firm:
GARRETT-WACKOWSKI, Eugenia et al. (US)
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