Conjugated hepcidin mimetics
AssigneeProtagonist Therapeutics, Inc.
InventorsDavid Y. Liu, Gregory Thomas Bourne, Roopa Taranath, Suneel Kumar Gupta, Nishit Bachulal Modi
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Abstract
The present invention provides hepcidin analogues, and related pharmaceutical compositions and use thereof in treating polycythemia vera.
Claims31
A method for treating polycythemia vera in a subject in need thereof, comprising administering to the subject an effective amount of a hepcidin analogue or a pharmaceutically acceptable salt or solvate thereof, wherein the hepcidin analogue comprises a peptide comprising or consisting of Formula I:
- (I)
- (SEQ ID NO:
- 1)
- R1-X-Y-R2
- wherein
- R1 is hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C1-C20 alkanoyl, or pGlu;
- R2 is NH2 or OH;
- X is a peptide sequence having Formula II
- (II)
- (SEQ ID NO:
- 2)
- Xl-X2-X3-X4-X5-X6-X7-X8-X9-X10
- wherein
- X1 is Asp, Ala, Ida, pGlu, bhAsp, Leu, D-Asp, or absent;
- X2 is Thr, Ala, or D-Thr;
- X3 is His, Lys, or D-His;
- X4 is Phe, Ala, Dpa, or D-Phe;
- X5 is Pro, Gly, Arg, Lys, Ala, D-Pro, or bhPro;
- X6 is Ile, Cys, Arg, Lys, D-Ile, or D-Cys;
- X7 is Cys, Ile, Leu, Val, Phe, D-Ile, or D-Cys;
- X8 is Ile, Arg, Phe, Gln, Lys, Glu, Val, Leu, or D-Ile;
- X9 is Phe or bhPhe;
- and
- X10 is Lys, Phe, or absent;
- wherein if Y is absent, X7 is Ile;
- and
- Y is a peptide sequence having Formula III
- (III)
- (SEQ ID NO:
- 3)
- Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15
- wherein
- Y1 is Gly, Cys, Ala, Phe, Pro, Glu, Lys, D-Pro, Val, Ser, or absent;
- Y2 is Pro, Ala, Cys, Gly, or absent;
- Y3 is Arg, Lys, Pro, Gly, His, Ala, Trp, or absent;
- Y4 is Ser, Arg, Gly, Trp, Ala, His, Tyr, or absent;
- Y5 is Lys, Met, Arg, Ala, or absent;
- Y6 is Gly, Ser, Lys, Ile, Ala, Pro, Val, or absent;
- Y7 is Trp, Lys, Gly, Ala, Ile, Val, or absent;
- Y8 is Val, Thr, Gly, Cys, Met, Tyr, Ala, Glu, Lys, Asp, Arg, or absent;
- Y9 is Cys, Tyr, or absent;
- Y10 is Met, Lys, Arg, Tyr, or absent;
- Y11 is Arg, Met, Cys, Lys, or absent;
- Y12 is Arg, Lys, Ala, or absent;
- Y13 is Arg, Cys, Lys, Val, or absent;
- Y14 is Arg, Lys, Pro, Cys, Thr, or absent;
- and
- Y15 is Thr, Arg, or absent;
- wherein said peptide comprising or consisting of Formula I is optionally PEGylated on R1, X, or Y, and
- wherein a side chain of an amino acid of the peptide is optionally conjugated to a lipophilic substituent or polymeric moiety.
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Dependencies are inferred from the claim text.