Title:
PEPTIDES FOR OPIOID TOLERANCE BY BLOCKING RECEPTORS DIMERIZATION
Document Type and Number:
WIPO Patent Application WO/2023/243698
Kind Code:
A1
Abstract:
Problem The purpose of the present invention is to provide a novel method for prevention and/or treatment of opioid tolerance or opioid dependence. Specifically, the purpose of the present invention is to develop peptide-based blockers to block MOR-DOR and KOR-DOR heterodimerization. In addition, the purpose of the present invention is to develop homodimer blockers for MOR, DOR, and KOR which modulate their downstream signaling without affecting their internalization. Solution The present invention is a prophylactic and/or therapeutic agent for the prevention and/or treatment of opioid tolerance or opioid dependence comprising the peptide which inhibits the dimer formation of the opioid receptor, wherein the above opioid receptor dimer is a heterodimer or a homodimer formed from one or two opioid receptors selected from the group consisting of the μ type (MOR), the κ type (KOR), and the δ type (DOR).
Inventors:
KUSUMI AKIHIRO (JP)
ZHOU PENG (JP)
ZHOU PENG (JP)
Application Number:
PCT/JP2023/022333
Publication Date:
December 21, 2023
Filing Date:
June 15, 2023
Export Citation:
Assignee:
OKINAWA INST SCIENCE & TECH SCHOOL CORP (JP)
International Classes:
A61K38/02; A61K38/04; A61K38/16; A61P25/04
Foreign References:
| CN110128527A | 2019-08-16 | |||
| US20050019841A1 | 2005-01-27 | |||
| US20140322306A1 | 2014-10-30 |
Other References:
SHAO-QIU HE; ZHEN-NING ZHANG; JI-SONG GUAN; HONG-RUI LIU; BO ZHAO; HAI-BO WANG; QIAN LI; HONG YANG; JIE LUO; ZI-YAN LI; QIONG WANG: "Facilitation of -Opioid Receptor Activity by Preventing -Opioid Receptor-Mediated Codegradation", NEURON, ELSEVIER, AMSTERDAM, NL, vol. 69, no. 1, 26 October 2010 (2010-10-26), AMSTERDAM, NL, pages 120 - 131, XP028150805, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2010.12.001
XIE WEI-YAN, HE YI, YANG YAN-RUI, LI YA-FANG, KANG KAI, XING BAO-MING, WANG YUN: "Disruption of Cdk5-Associated Phosphorylation of Residue Threonine-161 of the δ-Opioid Receptor: Impaired Receptor Function and Attenuated Morphine Antinociceptive Tolerance", THE JOURNAL OF NEUROSCIENCE, SOCIETY FOR NEUROSCIENCE, US, vol. 29, no. 11, 18 March 2009 (2009-03-18), US , pages 3551 - 3564, XP093118643, ISSN: 0270-6474, DOI: 10.1523/JNEUROSCI.0415-09.2009
ERIK C. B. JOHNSON; STEPHEN B. H. KENT: "Exploratory synthesis of peptide–α‐thioester segments spanning the polypeptide sequence of the δ‐opioid receptor, a G protein‐coupled receptor", BIOPOLYMERS, JOHN WILEY, HOBOKEN, USA, vol. 88, no. 3, 21 November 2006 (2006-11-21), Hoboken, USA, pages 340 - 349, XP071133777, ISSN: 0006-3525, DOI: 10.1002/bip.20639
ROSA MÒNICA, BECH-SERRA JOAN JOSEP, CANALS FRANCESC, ZAJAC JEAN MARIE, TALMONT FRANCK, ARSEQUELL GEMMA, VALENCIA GREGORIO: "Optimized Proteomic Mass Spectrometry Characterization of Recombinant Human μ-Opioid Receptor Functionally Expressed in Pichia pastoris Cell Lines", JOURNAL OF PROTEOME RESEARCH, AMERICAN CHEMICAL SOCIETY, vol. 14, no. 8, 7 August 2015 (2015-08-07), pages 3162 - 3173, XP093118645, ISSN: 1535-3893, DOI: 10.1021/acs.jproteome.5b00104
DRAKE CARRIE T., PATTERSON TERRELL A., SIMMONS MICHELE L., CHAVKIN CHARLES, MILNER TERESA A.: "Kappa opioid receptor-like immunoreactivity in guinea pig brain: Ultrastructural localization in presynaptic terminals in hippocampal formation", THE JOURNAL OF COMPARATIVE NEUROLOGY, WILEY-LISS, NEW YORK, NY, US, vol. 370, no. 3, 1 July 1996 (1996-07-01), US , pages 377 - 395, XP093118639, ISSN: 0021-9967, DOI: 10.1002/(SICI)1096-9861(19960701)370:3<377::AID-CNE8>3.0.CO;2-1
CEN BO, XIONG YING, MA LAN, PEI GANG: "Direct and Differential Interaction of β-Arrestins with the Intracellular Domains of Different Opioid Receptors", MOLECULAR PHARMACOLOGY, AMERICAN SOCIETY FOR PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, US, vol. 59, no. 4, 1 April 2001 (2001-04-01), US , pages 758 - 764, XP009551726, ISSN: 0026-895X, DOI: 10.1124/mol.59.4.758
CHRISTOFFERS K H; LI H; KEENAN S M; HOWELLS R D: "Purification and mass spectrometric analysis of the ÄmuÜ opioid receptor", MOLECULAR BRAIN RESEARCH, ELSEVIER SCIENCE BV, AMSTERDAM, NL, vol. 118, no. 1-2, 21 October 2003 (2003-10-21), NL , pages 119 - 131, XP009087483, ISSN: 0169-328X, DOI: 10.1016/j.molbrainres.2003.08.008
ZHANG LI, ZHANG JIANG-TAO, HANG LIHUA, LIU TONG: "Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective", FRONTIERS IN PHARMACOLOGY, FRONTIERS RESEARCH FOUNDATION, CH, vol. 11, 15 July 2020 (2020-07-15), CH , pages 1078, XP093118641, ISSN: 1663-9812, DOI: 10.3389/fphar.2020.01078
CECHOVA KRISTINA; LAN CHENYANG; MACIK MATUS; BARTHES NICOLAS P. F.; JUNG MANFRED; ULBRICH MAXIMILIAN H.: "Kappa but not delta or mu opioid receptors form homodimers at low membrane densities", CMLS CELLULAR AND MOLECULAR LIFE SCIENCES., BIRKHAUSER VERLAG, HEIDELBERG., DE, vol. 78, no. 23, 17 October 2021 (2021-10-17), DE , pages 7557 - 7568, XP037630460, ISSN: 1420-682X, DOI: 10.1007/s00018-021-03963-y
XIE WEI-YAN, HE YI, YANG YAN-RUI, LI YA-FANG, KANG KAI, XING BAO-MING, WANG YUN: "Disruption of Cdk5-Associated Phosphorylation of Residue Threonine-161 of the δ-Opioid Receptor: Impaired Receptor Function and Attenuated Morphine Antinociceptive Tolerance", THE JOURNAL OF NEUROSCIENCE, SOCIETY FOR NEUROSCIENCE, US, vol. 29, no. 11, 18 March 2009 (2009-03-18), US , pages 3551 - 3564, XP093118643, ISSN: 0270-6474, DOI: 10.1523/JNEUROSCI.0415-09.2009
ERIK C. B. JOHNSON; STEPHEN B. H. KENT: "Exploratory synthesis of peptide–α‐thioester segments spanning the polypeptide sequence of the δ‐opioid receptor, a G protein‐coupled receptor", BIOPOLYMERS, JOHN WILEY, HOBOKEN, USA, vol. 88, no. 3, 21 November 2006 (2006-11-21), Hoboken, USA, pages 340 - 349, XP071133777, ISSN: 0006-3525, DOI: 10.1002/bip.20639
ROSA MÒNICA, BECH-SERRA JOAN JOSEP, CANALS FRANCESC, ZAJAC JEAN MARIE, TALMONT FRANCK, ARSEQUELL GEMMA, VALENCIA GREGORIO: "Optimized Proteomic Mass Spectrometry Characterization of Recombinant Human μ-Opioid Receptor Functionally Expressed in Pichia pastoris Cell Lines", JOURNAL OF PROTEOME RESEARCH, AMERICAN CHEMICAL SOCIETY, vol. 14, no. 8, 7 August 2015 (2015-08-07), pages 3162 - 3173, XP093118645, ISSN: 1535-3893, DOI: 10.1021/acs.jproteome.5b00104
DRAKE CARRIE T., PATTERSON TERRELL A., SIMMONS MICHELE L., CHAVKIN CHARLES, MILNER TERESA A.: "Kappa opioid receptor-like immunoreactivity in guinea pig brain: Ultrastructural localization in presynaptic terminals in hippocampal formation", THE JOURNAL OF COMPARATIVE NEUROLOGY, WILEY-LISS, NEW YORK, NY, US, vol. 370, no. 3, 1 July 1996 (1996-07-01), US , pages 377 - 395, XP093118639, ISSN: 0021-9967, DOI: 10.1002/(SICI)1096-9861(19960701)370:3<377::AID-CNE8>3.0.CO;2-1
CEN BO, XIONG YING, MA LAN, PEI GANG: "Direct and Differential Interaction of β-Arrestins with the Intracellular Domains of Different Opioid Receptors", MOLECULAR PHARMACOLOGY, AMERICAN SOCIETY FOR PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, US, vol. 59, no. 4, 1 April 2001 (2001-04-01), US , pages 758 - 764, XP009551726, ISSN: 0026-895X, DOI: 10.1124/mol.59.4.758
CHRISTOFFERS K H; LI H; KEENAN S M; HOWELLS R D: "Purification and mass spectrometric analysis of the ÄmuÜ opioid receptor", MOLECULAR BRAIN RESEARCH, ELSEVIER SCIENCE BV, AMSTERDAM, NL, vol. 118, no. 1-2, 21 October 2003 (2003-10-21), NL , pages 119 - 131, XP009087483, ISSN: 0169-328X, DOI: 10.1016/j.molbrainres.2003.08.008
ZHANG LI, ZHANG JIANG-TAO, HANG LIHUA, LIU TONG: "Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective", FRONTIERS IN PHARMACOLOGY, FRONTIERS RESEARCH FOUNDATION, CH, vol. 11, 15 July 2020 (2020-07-15), CH , pages 1078, XP093118641, ISSN: 1663-9812, DOI: 10.3389/fphar.2020.01078
CECHOVA KRISTINA; LAN CHENYANG; MACIK MATUS; BARTHES NICOLAS P. F.; JUNG MANFRED; ULBRICH MAXIMILIAN H.: "Kappa but not delta or mu opioid receptors form homodimers at low membrane densities", CMLS CELLULAR AND MOLECULAR LIFE SCIENCES., BIRKHAUSER VERLAG, HEIDELBERG., DE, vol. 78, no. 23, 17 October 2021 (2021-10-17), DE , pages 7557 - 7568, XP037630460, ISSN: 1420-682X, DOI: 10.1007/s00018-021-03963-y
Attorney, Agent or Firm:
TSUKUNI & ASSOCIATES (JP)
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