Title:
PEPTIDE THERAPEUTICS FOR AUTOIMMUNE DISEASES AND INFLAMMATORY DISEASES
Document Type and Number:
WIPO Patent Application WO/2021/010621
Kind Code:
A1
Abstract:
The present invention relates to a peptide inhibiting a Toll-like receptor (TLR) signaling pathway. More specifically, the present invention relates to: a peptide that strongly binds to a TIR-containing molecule to inhibit the TLR, in particular, the TLR4 signaling pathway; a fusion peptide in which a cell-penetrating peptide is conjugated to said peptide; a TLR4 antagonist comprising said peptide or said fusion peptide; and a composition for preventing or treating autoimmune diseases or inflammatory diseases comprising said peptide or said fusion peptide. According to the present invention, said peptide exhibits an inhibitory effect on a wide range of TLR signaling pathways including TLR4, blocks MyD88- and TRIF-dependent TLR4 pathways, and has a substantial disease-alleviating effect in mouse models of rheumatoid arthritis, psoriasis, systemic lupus erythematosus, and non-alcoholic steatohepatitis, and thus can be usefully utilized as therapeutics for immune-related diseases and inflammatory diseases that require negative control of TLR.
Inventors:
CHOI SANG DUN (KR)
SUH CHANG HEE (KR)
KIM WOOK (KR)
SHAH MASAUD (KR)
ACHEK ASMA (KR)
KIM GIYOUNG (KR)
CHEONG JAE YOUN (KR)
KIM SOON SUN (KR)
SUH CHANG HEE (KR)
KIM WOOK (KR)
SHAH MASAUD (KR)
ACHEK ASMA (KR)
KIM GIYOUNG (KR)
CHEONG JAE YOUN (KR)
KIM SOON SUN (KR)
Application Number:
PCT/KR2020/008536
Publication Date:
January 21, 2021
Filing Date:
June 30, 2020
Export Citation:
Assignee:
UNIV AJOU IND ACADEMIC COOP FOUND (KR)
International Classes:
C07K7/08; A61K47/64
Foreign References:
| US20130203649A1 | 2013-08-08 | |||
| KR20180122940A | 2018-11-14 | |||
| KR20160140031A | 2016-12-07 |
Other References:
NCBI Reference Sequence: AAL05628.1 TIR domain containing adaptor protein TIRAP[Mus musculus] (20 September 2001) definition; and fasta
COUTURE LEAH A., PIAO WENJI, RU LISA W., VOGEL STEFANIE N., TOSHCHAKOV VLADIMIR Y.: "Targeting Toll-like Receptor (TLR) Signaling by Toll/Interleukin-1 Receptor (TIR) Domain-containing Adapter Protein/MyD88 Adapter-like (TIRAP/Mal)-derived Decoy Peptides", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 287, no. 29, 1 July 2012 (2012-07-01), pages 24641 - 24648, XP055774156, ISSN: 0021-9258, DOI: 10.1074/jbc.M112.360925
SHAH MASAUD; KIM GI-YOUNG; ACHEK ASMA; CHO EUN-YOUNG; BAEK WOOK-YOUNG; CHOI YANG SEON; LEE WANG HEE; KIM DONG-JIN; LEE SANG HO; KI: "The αC helix of TIRAP holds therapeutic potential in TLR-mediated autoimmune diseases", BIOMATERIALS, ELSEVIER, AMSTERDAM, NL, vol. 245, 17 March 2020 (2020-03-17), AMSTERDAM, NL, XP086118035, ISSN: 0142-9612, DOI: 10.1016/j.biomaterials.2020.119974
AKIRA, S.UEMATSU, S.TAKEUCHI, O., CELL, vol. 124, 2006, pages 783 - 801
GAY, N. J. ET AL., NAT REV IMMUNOL, vol. 14, 2014, pages 546 - 558
CHEN, CJ ET AL., NAT MED, vol. 13, 2007, pages 851 - 856
GUVEN-MAIOROV, E. ET AL., SCI REP, vol. 5, 2015, pages 15623
BOVIJN, C. ET AL., JBIOL CHEM, vol. 288, 2013, pages 12054 - 12066
COUTURE, L. A. ET AL., J BIOL CHEM, vol. 287, 2012, pages 24641 - 24648
LIN, Z. ET AL., PLOS ONE, vol. 7, 2012, pages e34202
HARRISON, R. S. ET AL., PROC NATL ACAD SCI USA, vol. 107, 2010, pages 11686 - 11691
MONIE, T. P. ET AL., IMMUNOL REV, vol. 227, 2009, pages 161 - 175
PARK, B.S ET AL., EXP. MOL. MED., vol. 45, 2013, pages e66
NIJLAND, R ET AL., MAR. DRUGS, vol. 12, 2014, pages 4260 - 4273
ACHEK, A ET AL., ARCH. PHARMACOL RES., vol. 39, 2016, pages 1032 - 1049
KAWAI,T ET AL., NAT. IMMUNOL., vol. 11, 2010, pages 373 - 384
KIM, J.Y ET AL., EUR. J. PHARMACOL., vol. 584, 2008, pages 175 - 184
LIU, K.-L. ET AL., J. AGRIC. FOOD CHEM., vol. 54, 2006, pages 3472 - 3478
WEST, A. P. ET AL., NATURE, vol. 472, 2011, pages 476 - 480
NEWLAND, A. ET AL., BRITISH JOURNAL OF HAEMATOLOGY, vol. 135, 2006, pages 547 - 553
HOPKINS, A. L.GROOM, C. R., NAT REV DRUG DISCOV, vol. 1, 2002, pages 727 - 730
KWON, H. K. ET AL., TOXICOLOGICAL SCIENCES: AN OFFICIAL JOURNAL OF THE SOCIETY OF TOXICOLOGY, vol. 148, 2015, pages 204 - 219
RHEE, M.DAVIS, P., J BIOL CHEM, vol. 281, 2006, pages 1233 - 1240
DEROSSI, D. ET AL., JBIOL CHEM, vol. 269, 1994, pages 10444 - 10450
YAMAMOTO, M. ET AL., NATURE, vol. 420, 2002, pages 324 - 329
PIAO, W. ET AL., J IMMUNOL, vol. 190, 2013, pages 2263 - 2272
YAMAMOTO, M. ET AL., SCIENCE, vol. 301, 2003, pages 640 - 643
HONDA, K.TANIGUCHI, T., NAT REV IMMUNOL, vol. 6, 2006, pages 644 - 658
BAUERNFEIND, F. G. ET AL., JLMMUNOL, vol. 183, 2009, pages 787 - 791
FITZGERALD, K. A. ET AL., JEXPMED, vol. 198, 2003, pages 1043 - 1055
STEVENS, S. L. ET AL., JNEUROSCI, vol. 31, 2011, pages 8456 - 8463
HIRAI, T. ET AL., JLMMUNOL, vol. 190, 2013, pages 4805 - 4811
CARCELLER, E. ET AL., SCI REP, vol. 6, 2016, pages 38825
WU, Y. W.TANG, W.ZUO, J. P., ACTA PHARMACOL SIN, vol. 36, 2015, pages 1395 - 1407
TOLLER-KAWAHISA, J. E. ET AL., FREE RADIC BIOL MED, vol. 86, 2015, pages 362 - 373
BASHAL, F., OPEN RHEUMATOL J, vol. 7, 2013, pages 87 - 95
SANDHU, V.QUAN, M., OPEN RHEUMATOL J, vol. 12, 2018, pages 171
RIVERA CA ET AL., JHEPATOL, vol. 47, 2007, pages 571 - 579
ROH YS ET AL., THE AMERICAN JOURNAL OF PATHOLOGY, vol. 188, pages 2574 - 2588
COUTURE LEAH A., PIAO WENJI, RU LISA W., VOGEL STEFANIE N., TOSHCHAKOV VLADIMIR Y.: "Targeting Toll-like Receptor (TLR) Signaling by Toll/Interleukin-1 Receptor (TIR) Domain-containing Adapter Protein/MyD88 Adapter-like (TIRAP/Mal)-derived Decoy Peptides", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 287, no. 29, 1 July 2012 (2012-07-01), pages 24641 - 24648, XP055774156, ISSN: 0021-9258, DOI: 10.1074/jbc.M112.360925
SHAH MASAUD; KIM GI-YOUNG; ACHEK ASMA; CHO EUN-YOUNG; BAEK WOOK-YOUNG; CHOI YANG SEON; LEE WANG HEE; KIM DONG-JIN; LEE SANG HO; KI: "The αC helix of TIRAP holds therapeutic potential in TLR-mediated autoimmune diseases", BIOMATERIALS, ELSEVIER, AMSTERDAM, NL, vol. 245, 17 March 2020 (2020-03-17), AMSTERDAM, NL, XP086118035, ISSN: 0142-9612, DOI: 10.1016/j.biomaterials.2020.119974
AKIRA, S.UEMATSU, S.TAKEUCHI, O., CELL, vol. 124, 2006, pages 783 - 801
GAY, N. J. ET AL., NAT REV IMMUNOL, vol. 14, 2014, pages 546 - 558
CHEN, CJ ET AL., NAT MED, vol. 13, 2007, pages 851 - 856
GUVEN-MAIOROV, E. ET AL., SCI REP, vol. 5, 2015, pages 15623
BOVIJN, C. ET AL., JBIOL CHEM, vol. 288, 2013, pages 12054 - 12066
COUTURE, L. A. ET AL., J BIOL CHEM, vol. 287, 2012, pages 24641 - 24648
LIN, Z. ET AL., PLOS ONE, vol. 7, 2012, pages e34202
HARRISON, R. S. ET AL., PROC NATL ACAD SCI USA, vol. 107, 2010, pages 11686 - 11691
MONIE, T. P. ET AL., IMMUNOL REV, vol. 227, 2009, pages 161 - 175
PARK, B.S ET AL., EXP. MOL. MED., vol. 45, 2013, pages e66
NIJLAND, R ET AL., MAR. DRUGS, vol. 12, 2014, pages 4260 - 4273
ACHEK, A ET AL., ARCH. PHARMACOL RES., vol. 39, 2016, pages 1032 - 1049
KAWAI,T ET AL., NAT. IMMUNOL., vol. 11, 2010, pages 373 - 384
KIM, J.Y ET AL., EUR. J. PHARMACOL., vol. 584, 2008, pages 175 - 184
LIU, K.-L. ET AL., J. AGRIC. FOOD CHEM., vol. 54, 2006, pages 3472 - 3478
WEST, A. P. ET AL., NATURE, vol. 472, 2011, pages 476 - 480
NEWLAND, A. ET AL., BRITISH JOURNAL OF HAEMATOLOGY, vol. 135, 2006, pages 547 - 553
HOPKINS, A. L.GROOM, C. R., NAT REV DRUG DISCOV, vol. 1, 2002, pages 727 - 730
KWON, H. K. ET AL., TOXICOLOGICAL SCIENCES: AN OFFICIAL JOURNAL OF THE SOCIETY OF TOXICOLOGY, vol. 148, 2015, pages 204 - 219
RHEE, M.DAVIS, P., J BIOL CHEM, vol. 281, 2006, pages 1233 - 1240
DEROSSI, D. ET AL., JBIOL CHEM, vol. 269, 1994, pages 10444 - 10450
YAMAMOTO, M. ET AL., NATURE, vol. 420, 2002, pages 324 - 329
PIAO, W. ET AL., J IMMUNOL, vol. 190, 2013, pages 2263 - 2272
YAMAMOTO, M. ET AL., SCIENCE, vol. 301, 2003, pages 640 - 643
HONDA, K.TANIGUCHI, T., NAT REV IMMUNOL, vol. 6, 2006, pages 644 - 658
BAUERNFEIND, F. G. ET AL., JLMMUNOL, vol. 183, 2009, pages 787 - 791
FITZGERALD, K. A. ET AL., JEXPMED, vol. 198, 2003, pages 1043 - 1055
STEVENS, S. L. ET AL., JNEUROSCI, vol. 31, 2011, pages 8456 - 8463
HIRAI, T. ET AL., JLMMUNOL, vol. 190, 2013, pages 4805 - 4811
CARCELLER, E. ET AL., SCI REP, vol. 6, 2016, pages 38825
WU, Y. W.TANG, W.ZUO, J. P., ACTA PHARMACOL SIN, vol. 36, 2015, pages 1395 - 1407
TOLLER-KAWAHISA, J. E. ET AL., FREE RADIC BIOL MED, vol. 86, 2015, pages 362 - 373
BASHAL, F., OPEN RHEUMATOL J, vol. 7, 2013, pages 87 - 95
SANDHU, V.QUAN, M., OPEN RHEUMATOL J, vol. 12, 2018, pages 171
RIVERA CA ET AL., JHEPATOL, vol. 47, 2007, pages 571 - 579
ROH YS ET AL., THE AMERICAN JOURNAL OF PATHOLOGY, vol. 188, pages 2574 - 2588
Attorney, Agent or Firm:
LEE, Cheo Young et al. (KR)
Download PDF: