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US 2023/0146455 A1Published application
Treatment of inflammatory diseases with peptides and pharmaceutical compositions
AssigneeYuyu Pharma, Inc.
InventorsWonsang Yu, Larry Chong Park
Life of this patent
Estimating the term…
Abstract
Disclosed are methods of treating inflammatory diseases with peptides and pharmaceutical compositions using peptides.
Claims261
A method of preventing or treating an IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, MMP3, CCL-2, CCL-3, CCL-4, Fas, TIMP-1, or a Th1, Th2, and/or Th17 derived cytokine or proinflammatory chemokine mediated disease or disorder in a subject, comprising administering to the subject
- i) a compound represented by Formula (I), (V), (VI), (VII), (IX) or (X-am) or a pharmaceutically acceptable salt and/or prodrug thereof:
- wherein:
- R1, R2, and R3 are each independently H or substituted or unsubstituted alkyl, alkoxy, haloalkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl;
- R4, independently for each occurrence, is selected from substituted or unsubstituted alkyl, aryl, arylalkyl, heterocycloalkyl, oxo, —ORb, —CH2ORb, halo, hydroxyl, and hydroxyalkyl;
- Rb is substituted or unsubstituted alkyl, aryl, arylalkyl, or heterocycloalkyl;
- p is 0, 1, or 2;
- R6 is hydrogen or substituted or unsubstituted alkyl;
- R7, R8, and R9 are each independently hydrogen or alkyl;
- J is OH or —NRxRy;
- and
- Rx and Ry are each independently selected from H, optionally substituted alkyl, optionally substituted alkoxylalkyl, or Rx and Ry taken together with the intervening nitrogen atom form a ring,
- ii) a compound represented by Formula (8) or (10)
- or a pharmaceutically acceptable salt and/or prodrug thereof:
- iii) a peptide having an amino acid sequence represented by HyP-Gly-Gln-Xaa-Gly-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Asp-Xbb-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Xcc or Xdd-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys, or a pharmaceutically acceptable salt and/or stereoisomer thereof,
- wherein:
- Xaa is selected from Glu, Asn, Gln, His, Lys, Ser, Thr, Ala, Val, Ile, Leu, Phe, Tyr, Trp, homo-Ser, Asp(Me), and Asn(Me);
- Xbb is selected from Val, Ile, Leu, Ala, Phe, Tyr, Trp, Ser, Thr, and (N-Me)Gly;
- Xcc is selected from Tyr, Leu, Glu, Gln, Ala, and Nle(6-OH);
- and
- Xdd is selected from:
- or
- iv) a peptide having any one amino acid sequence selected from:
- Ala-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys;
- Hyp-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Ala-Lys;
- HyP-Gly-Gln-Leu-Gly-Leu-Ala;
- HyP-Gly-Gln-Glu-Gly-Leu-Gly;
- HyP-Gly-Gln-Leu-Gly-Leu;
- D-HyP(2R, 4S)-Gly-D-Gln-D-Leu-Gly-D-Leu;
- HyP-Gly-Gln-Leu-Gly, HyP-Gly-Gln-D-Leu-Gly;
- and
- D-HyP(2R, 4S)-Gly-Gln-Leu-Gly.
28 more elements
A method of reducing production of IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α, MMP3, CCL-2, CCL-3, CCL-4, Fas, TIMP-1, or a Th1, Th2, and/or Th17 derived cytokine or proinflammatory chemokine in cells of a subject, comprising administering to a subject
- i) a compound represented by Formula (I), (V), (VI), (VII), (IX) or (X-am) or a pharmaceutically acceptable salt and/or prodrug thereof:
- wherein:
- R1, R2, and R3 are each independently H or substituted or unsubstituted alkyl, alkoxy, haloalkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl;
- R4, independently for each occurrence, is selected from substituted or unsubstituted alkyl, aryl, arylalkyl, heterocycloalkyl, oxo, —ORb, —CH2ORb, halo, hydroxyl, and hydroxyalkyl;
- Rb is substituted or unsubstituted alkyl, aryl, arylalkyl, or heterocycloalkyl;
- p is 0, 1, or 2;
- R6 is hydrogen or substituted or unsubstituted alkyl;
- R7, R8, and R9 are each independently hydrogen or alkyl;
- J is OH or —NRxRy;
- and
- Rx and Ry are each independently selected from H, optionally substituted alkyl, optionally substituted alkoxylalkyl, or Rx and Ry taken together with the intervening nitrogen atom form a ring,
- ii) a compound represented by Formula (8) or (10)
- or a pharmaceutically acceptable salt and/or prodrug thereof:
- iii) a peptide having an amino acid sequence represented by HyP-Gly-Gln-Xaa-Gly-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Asp-Xbb-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Xcc or Xdd-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys, or a pharmaceutically acceptable salt and/or stereoisomer thereof,
- wherein:
- Xaa is selected from Glu, Asn, Gln, His, Lys, Ser, Thr, Ala, Val, Ile, Leu, Phe, Tyr, Trp, homo-Ser, Asp(Me), and Asn(Me);
- Xbb is selected from Val, Ile, Leu, Ala, Phe, Tyr, Trp, Ser, Thr, and (N-Me)Gly;
- Xcc is selected from Tyr, Leu, Glu, Gln, Ala, and Nle(6-OH);
- and
- Xdd is selected from:
- or
- iv) a peptide having any one amino acid sequence selected from:
- Ala-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys;
- Hyp-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Ala-Lys;
- HyP-Gly-Gln-Leu-Gly-Leu-Ala;
- HyP-Gly-Gln-Glu-Gly-Leu-Gly;
- HyP-Gly-Gln-Leu-Gly-Leu;
- D-HyP(2R, 4S)-Gly-D-Gln-D-Leu-Gly-D-Leu;
- HyP-Gly-Gln-Leu-Gly, HyP-Gly-Gln-D-Leu-Gly;
- and
- D-HyP(2R, 4S)-Gly-Gln-Leu-Gly.
28 more elements
A method of reducing NF-κB transcription activity in cells of a subject, comprising administering to a subject
- i) a compound represented by Formula (I), (V), (VI), (VII), (IX) or (X-am) or a pharmaceutically acceptable salt and/or prodrug thereof:
- wherein:
- R1, R2, and R3 are each independently H or substituted or unsubstituted alkyl, alkoxy, haloalkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl;
- R4, independently for each occurrence, is selected from substituted or unsubstituted alkyl, aryl, arylalkyl, heterocycloalkyl, oxo, —ORb, —CH2ORb, halo, hydroxyl, and hydroxyalkyl;
- Rb is substituted or unsubstituted alkyl, aryl, arylalkyl, or heterocycloalkyl;
- p is 0, 1, or 2;
- R6 is hydrogen or substituted or unsubstituted alkyl;
- R7, R8, and R9 are each independently hydrogen or alkyl;
- J is OH or —NRxRy;
- and
- Rx and Ry are each independently selected from H, optionally substituted alkyl, optionally substituted alkoxylalkyl, or Rx and Ry taken together with the intervening nitrogen atom form a ring,
- ii) a compound represented by Formula 8 or 10
- or a pharmaceutically acceptable salt and/or prodrug thereof:
- iii) a peptide having an amino acid sequence represented by HyP-Gly-Gln-Xaa-Gly-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Asp-Xbb-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Xcc or Xdd-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys, or a pharmaceutically acceptable salt and/or stereoisomer thereof,
- wherein:
- Xaa is selected from Glu, Asn, Gln, His, Lys, Ser, Thr, Ala, Val, Ile, Leu, Phe, Tyr, Trp, homo-Ser, Asp(Me), and Asn(Me);
- Xbb is selected from Val, Ile, Leu, Ala, Phe, Tyr, Trp, Ser, Thr, and (N-Me)Gly;
- Xcc is selected from Tyr, Leu, Glu, Gln, Ala, and Nle(6-OH);
- and
- Xdd is selected from:
- or
- iv) a peptide having any one amino acid sequence selected from:
- Ala-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys;
- Hyp-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Ala-Lys;
- HyP-Gly-Gln-Leu-Gly-Leu-Ala;
- HyP-Gly-Gln-Glu-Gly-Leu-Gly;
- HyP-Gly-Gln-Leu-Gly-Leu;
- D-HyP(2R, 4S)-Gly-D-Gln-D-Leu-Gly-D-Leu;
- HyP-Gly-Gln-Leu-Gly, HyP-Gly-Gln-D-Leu-Gly;
- and
- D-HyP(2R, 4S)-Gly-Gln-Leu-Gly.
28 more elements
A method of preventing or treating Keratoconjunctivitis sicca (Dry Eye) in a subject, comprising administering to the subject
- i) a compound represented by Formula (I), (V), (VI), (VII), (IX) or (X-am) or a pharmaceutically acceptable salt and/or prodrug thereof:
- wherein:
- R1, R2, and R3 are each independently H or substituted or unsubstituted alkyl, alkoxy, haloalkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl;
- R4, independently for each occurrence, is selected from substituted or unsubstituted alkyl, aryl, arylalkyl, heterocycloalkyl, oxo, —ORb, —CH2ORb, halo, hydroxyl, and hydroxyalkyl;
- Rb is substituted or unsubstituted alkyl, aryl, arylalkyl, or heterocycloalkyl;
- p is 0, 1, or 2;
- R6 is hydrogen or substituted or unsubstituted alkyl;
- R7, R8, and R9 are each independently hydrogen or alkyl;
- J is OH or —NRxRy;
- and
- Rx and Ry are each independently selected from H, optionally substituted alkyl, optionally substituted alkoxylalkyl, or Rx and Ry taken together with the intervening nitrogen atom form a ring,
- ii) a compound represented by Formula (8) or (10)
- or a pharmaceutically acceptable salt and/or prodrug thereof:
- iii) a peptide having an amino acid sequence represented by HyP-Gly-Gln-Xaa-Gly-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Asp-Xbb-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Xcc or Xdd-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys, or a pharmaceutically acceptable salt and/or stereoisomer thereof, wherein:
- Xaa is selected from Glu, Asn, Gln, His, Lys, Ser, Thr, Ala, Val, Ile, Leu, Phe, Tyr, Trp, homo-Ser, Asp(Me), and Asn(Me);
- Xbb is selected from Val, Ile, Leu, Ala, Phe, Tyr, Trp, Ser, Thr, and (N-Me)Gly;
- Xcc is selected from Tyr, Leu, Glu, Gln, Ala, and Nle(6-OH);
- and
- Xdd is selected from:
- or
- iv) a peptide having any one amino acid sequence selected from:
- Ala-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys;
- Hyp-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Ala-Lys;
- HyP-Gly-Gln-Leu-Gly-Leu-Ala;
- HyP-Gly-Gln-Glu-Gly-Leu-Gly;
- HyP-Gly-Gln-Leu-Gly-Leu;
- D-HyP(2R, 4S)-Gly-D-Gln-D-Leu-Gly-D-Leu;
- HyP-Gly-Gln-Leu-Gly, HyP-Gly-Gln-D-Leu-Gly;
- and
- D-HyP(2R, 4S)-Gly-Gln-Leu-Gly.
27 more elements
A method of preventing or treating Dry Eye Disease (DED) in a subject, comprising administering to the subject
- i) a compound represented by Formula (I), (V), (VI), (VII), (IX) or (X-am) or a pharmaceutically acceptable salt and/or prodrug thereof:
- wherein:
- R1, R2, and R3 are each independently H or substituted or unsubstituted alkyl, alkoxy, haloalkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl;
- R4, independently for each occurrence, is selected from substituted or unsubstituted alkyl, aryl, arylalkyl, heterocycloalkyl, oxo, —ORb, —CH2ORb, halo, hydroxyl, and hydroxyalkyl;
- Rb is substituted or unsubstituted alkyl, aryl, arylalkyl, or heterocycloalkyl;
- p is 0, 1, or 2;
- R6 is hydrogen or substituted or unsubstituted alkyl;
- R7, R8, and R9 are each independently hydrogen or alkyl;
- J is OH or —NRxRy;
- and
- Rx and Ry are each independently selected from H, optionally substituted alkyl, optionally substituted alkoxylalkyl, or Rx and Ry taken together with the intervening nitrogen atom form a ring,
- ii) a compound represented by Formula (8) or (10)
- or a pharmaceutically acceptable salt and/or prodrug thereof:
- iii) a peptide having an amino acid sequence represented by HyP-Gly-Gln-Xaa-Gly-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Asp-Xbb-Leu-Ala-Gly-Pro-Lys, HyP-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Xcc or Xdd-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys, or a pharmaceutically acceptable salt and/or stereoisomer thereof, wherein:
- Xaa is selected from Glu, Asn, Gln, His, Lys, Ser, Thr, Ala, Val, Ile, Leu, Phe, Tyr, Trp, homo-Ser, Asp(Me), and Asn(Me);
- Xbb is selected from Val, Ile, Leu, Ala, Phe, Tyr, Trp, Ser, Thr, and (N-Me)Gly;
- Xcc is selected from Tyr, Leu, Glu, Gln, Ala, and Nle(6-OH);
- and
- Xdd is selected from:
- or
- iv) a peptide having any one amino acid sequence selected from:
- Ala-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Pro-Lys;
- Hyp-Gly-Gln-Leu-Gly-Leu-Ala-Gly-Ala-Lys;
- HyP-Gly-Gln-Leu-Gly-Leu-Ala;
- HyP-Gly-Gln-Glu-Gly-Leu-Gly;
- HyP-Gly-Gln-Leu-Gly-Leu;
- D-HyP(2R, 4S)-Gly-D-Gln-D-Leu-Gly-D-Leu;
- HyP-Gly-Gln-Leu-Gly, HyP-Gly-Gln-D-Leu-Gly;
- and
- D-HyP(2R, 4S)-Gly-Gln-Leu-Gly.
27 more elements
Dependencies are inferred from the claim text.