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Thrombopoietic compounds

  • US 8,044,174 B2
  • Filed: 09/02/2004
  • Issued: 10/25/2011
  • Est. Priority Date: 10/23/1998
  • Status: Expired due to Fees
First Claim
Patent Images

1. A compound that binds to an mpl receptor comprising the structure
TMP1-(L1)n-TMP2 wherein the C-terminus of the TMP1 peptide is linked to the N-terminus of the TMP2 peptide, optionally via L1,wherein TMP1 and TMP2 are each independently selected from the group of core compounds comprising the structure selected from the group consisting of:

  • a) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Lys, and Val;

    X3 is selected from the group consisting of Gly and Ala;

    X4 is Pro;

    X5 is selected from the group consisting of Thr and Ser;

    X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

    X7 is selected from the group consisting of Arg and Lys;

    X8 is selected from the group consisting of Gln, Asn, and Glu;

    X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys;

    b) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Asp, Lys, and Val;

    X3 is Ala;

    X4 is Pro;

    X5 is selected from the group consisting of Thr and Ser;

    X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

    X7 is selected from the group consisting of Arg and Lys;

    X8 is selected from the group consisting of Gln, Asn, and Glu;

    X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys;

    C) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Asp, Lys, and Val;

    X3 is selected from the group consisting of Gly and Ala;

    X4 is Pro;

    X5 is Ser;

    X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

    X7 is selected from the group consisting of Arg and Lys;

    X8 is selected from the group consisting of Gln, Asn, and Glu;

    X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys;

    d) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Asp, Lys, and Val;

    X3 is selected from the group consisting of Gly and Ala;

    X4 is Pro;

    X5 is selected from the group consisting of Thr and Ser;

    X6 is selected from the group consisting of Ile, Val, Ala, and Phe;

    X7 is selected from the group consisting of Arg and Lys;

    X8 is selected from the group consisting of Gln, Asn, and Glu;

    X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys;

    e) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Asp, Lys, and Val;

    X3 is selected from the group consisting of Gly and Ala;

    X4 is Pro;

    X5 is selected from the group consisting of Thr and Ser;

    X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

    X7 is Lys;

    X8 is selected from the group consisting of Gln, Asn, and Glu;

    X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys;

    f) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Asp, Lys, and Val;

    X3 is selected from the group consisting of Gly and Ala;

    X4 is Pro;

    X5 is selected from the group consisting of Thr and Ser;

    X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

    X7 is selected from the group consisting of Arg and Lys;

    X8 is selected from the group consisting of Gln and Asn;

    X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys;

    g) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Asp, Lys, and Val;

    X3 is selected from the group consisting of Gly and Ala;

    X4 is Pro;

    X5 is selected from the group consisting of Thr and Ser;

    X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

    X7 is selected from the group consisting of Arg and Lys;

    X8 is selected from the group consisting of Gln, Asn, and Glu;

    X9 is selected from the group consisting of Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Ile, Val, Ala, Phe, Met, and Lys; and

    h) X2-X3-X4-X5-X6-X7-X8-X9-X10,wherein,X2 is selected from the group consisting of Glu, Asp, Lys, and Val;

    X3 is selected from the group consisting of Gly and Ala;

    X4 is Pro;

    X5 is selected from the group consisting of Thr and Ser;

    X6 is selected from the group consisting of Leu, Ile, Val, Ala, and Phe;

    X7 is selected from the group consisting of Arg and Lys;

    X8 is selected from the group consisting of Gln, Asn, and Glu;

    X9 is selected from the group consisting of Trp, Tyr, Cys, Ala, and Phe;

    X10 is selected from the group consisting of Leu, Val, Ala, Phe, Met, and Lys; and

    wherein L1 is a linker; and

    n is 0 or 1, wherein when n is 1, L1 is independently selected from the linker groups consisting of Yn, wherein Y is a naturally occurring amino acid or a stereoisomer thereof and n is 1 through 20;

    and physiologically acceptable salts thereof.

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