Title:
CYCLIC PEPTIDE OR SALT THEREOF AND MDMX INHIBITOR
Document Type and Number:
WIPO Patent Application WO/2024/043249
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing a cyclic peptide or salt thereof having excellent cell membrane permeability and excellent target bindability with MDMX, and an MDMX inhibitor. The present invention provides a cyclic peptide, or a salt thereof, which is represented by formula (1) defined in the specification of the present application, and which has features (a)-(d) below. (a) The cyclic peptide has a structure in which, when a is taken to be the axial length in the axial direction of the longest main chain structure and b and c are taken to be the axial lengths in two other directions which are orthogonal to a and orthogonal to each other, and the ellipsoid approximation is performed to determine the axial lengths for a, b, and c, and through this approximation stage, the molecular shape factor r is calculated using formula (2), r ranges from 0.4 to 0.6. (b) The aforementioned peptide is nonionic under a physiological environment. (c) The proportion of the number of N-substituted amino acids to the total number of amino acids in the aforementioned peptide is 25% or more. (d) The aforementioned peptide includes 1-3 amino acid residues and amino acid analogue residues having an aromatic carbocyclic group or an aromatic heterocyclic group in a side chain.
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Inventors:
KANEKO MAI (JP)
TAMURA TAKASHI (JP)
SUZUKI KOO (JP)
TSUMURA KYOSUKE (JP)
OHASHI NORIYUKI (JP)
KOCHI MASAHIRO (JP)
HASHIMOTO ICHIHIKO (JP)
MIYAHARA KENTA (JP)
HORIGOME HIROKI (JP)
TAMURA TAKASHI (JP)
SUZUKI KOO (JP)
TSUMURA KYOSUKE (JP)
OHASHI NORIYUKI (JP)
KOCHI MASAHIRO (JP)
HASHIMOTO ICHIHIKO (JP)
MIYAHARA KENTA (JP)
HORIGOME HIROKI (JP)
Application Number:
PCT/JP2023/030222
Publication Date:
February 29, 2024
Filing Date:
August 23, 2023
Export Citation:
Assignee:
FUJIFILM CORP (JP)
International Classes:
C07K4/00; C07K7/64; C12N15/11
Domestic Patent References:
| WO2021102322A1 | 2021-05-27 |
Foreign References:
| US20220002346A1 | 2022-01-06 |
Other References:
FURUKAWA, A. ET AL.: "Drug-Like Properties in Macrocycles above MW 1000: Backbone Rigidity versus Side-Chain Lipophilicity", ANGEWANDTE CHEMIE, vol. 59, no. 48, 2020, pages 21571 - 21577, XP072094457, DOI: 10.1002/anie.202004550
PYE, C. R. ET AL.: "Nonclassical Size Dependence of Permeation Defines Bounds for Passive Adsorption of Large Drug Molecules", JOURNAL OF MEDICINAL CHEMISTRY, vol. 60, no. 5, 2017, pages 1665 - 1672, XP093142676, DOI: 10.1021/acs.jmedchem.6b01483
FOUCHE, M. ET AL.: "Pharmacokinetic Studies around the Mono-and Difunctionalization of a Bioavailable Cyclic Decapeptide Scaffold", CHEMMEDCHEM, vol. 11, no. 10, 2016, pages 1060 - 1068, XP072415375, DOI: 10.1002/cmdc.201600083
LAWRENCE, N. ET AL.: "Cyclic peptide scaffold with ability to stabilize and deliver a helical cell -impermeable cargo across membranes of cultured cancer cells.", RSC CHEMICAL BIOLOGY, vol. 1, 2020, pages 405 - 420, XP093142681, DOI: 10.1039/d0cb00099j
PARTRIDGE, A. W. ET AL.: "Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties", MOLECULES, vol. 24, no. 12, 2019, pages 2292, XP093142680, DOI: 10.3390/molecules24122292
PYE, C. R. ET AL.: "Nonclassical Size Dependence of Permeation Defines Bounds for Passive Adsorption of Large Drug Molecules", JOURNAL OF MEDICINAL CHEMISTRY, vol. 60, no. 5, 2017, pages 1665 - 1672, XP093142676, DOI: 10.1021/acs.jmedchem.6b01483
FOUCHE, M. ET AL.: "Pharmacokinetic Studies around the Mono-and Difunctionalization of a Bioavailable Cyclic Decapeptide Scaffold", CHEMMEDCHEM, vol. 11, no. 10, 2016, pages 1060 - 1068, XP072415375, DOI: 10.1002/cmdc.201600083
LAWRENCE, N. ET AL.: "Cyclic peptide scaffold with ability to stabilize and deliver a helical cell -impermeable cargo across membranes of cultured cancer cells.", RSC CHEMICAL BIOLOGY, vol. 1, 2020, pages 405 - 420, XP093142681, DOI: 10.1039/d0cb00099j
PARTRIDGE, A. W. ET AL.: "Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties", MOLECULES, vol. 24, no. 12, 2019, pages 2292, XP093142680, DOI: 10.3390/molecules24122292
Attorney, Agent or Firm:
SIKS & CO. (JP)
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