Back to results
US 2023/0143604 A1Published application
Qw dosing of gip receptor agonist peptide compounds and uses thereof
AssigneeTakeda Pharmaceutical Company Limited
InventorsAntoine Charles Olivier HENNINOT, Derek Cecil COLE, Nicholas SCORAH
Life of this patent
Estimating the term…
Abstract
The present disclosure provides GIP receptor agonist peptide compounds suitable for once per week dosing (QW), said peptide compounds having an activating action on GIP receptors and use of the GIP receptor agonist peptide as a medicament for the treatment and/or prevention of emesis, or a symptom or condition associated with emesis. Specifically, a GIP receptor agonist peptide containing a sequence represented by any of the formulas (I)-(V) or a salt thereof, and a medicament comprising the same are provided.
Claims57
A GIP receptor agonist peptide represented by formula (I):
- P1-Tyr-A2-Glu-Gly-Thr-Phe-Ile-Ser-A9-Tyr-Ser-Ile-A13-A14-Asp-A16-A17-A18-Gln-A20-A21-Phe-Val-A24-Trp-Leu-Leu-Ala-Gln-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-A40-A41-A42-P2, or a pharmaceutically acceptable salt thereof;
- wherein
- P1 represents a group represented by formula
- —RA1,
- —CO—RA1,
- —CO—ORA1,
- —CO—CORA1,
- —SO—RA1,
- —SO2—RA1,
- —SO2—ORA1,
- —CO—NRA2RA3,
- —SO2—NRA2RA3,
- —C(═NRA1)—NRA2RA3, or
- is absent,
- wherein RA1, RA2, and RA3 each independently represent a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;
- P2 represents —NH2 or —OH;
- A2:
- represents Aib, D-Ala, Ala, Gly, or Pro;
- A9:
- represents Asp or Leu;
- A13:
- represents Aib, or Ala;
- A14:
- represents Leu, Aib, Ile, or Nle;
- A16:
- represents Arg, Ser, or Lys;
- A17:
- represents Aib, Ala, or Ile;
- A18:
- represents Ala, His, or Lys;
- A19:
- represents Gln, or Ala;
- A20:
- represents Aib, Gln, or Ala;
- A21:
- represents Asp, Asn, or Lys;
- A24:
- represents Asn, Gln, or Glu;
- A30:
- represents Arg, Ser, Gln, or Lys;
- A31:
- represents Gly, Pro, or a deletion;
- A32:
- represents Ser, Lys, Pro, Gly, or a deletion;
- A33:
- represents Ser, Lys, Gly, or a deletion;
- A34:
- represents Gly, Asn, or a deletion;
- A35:
- represents Ala, Asp, Ser, Asn, or a deletion;
- A36:
- represents Pro, Trp, or a deletion;
- A37:
- represents Pro, Lys, or a deletion;
- A38:
- represents Pro, His, or a deletion;
- A39:
- represents Ser, Asn, or a deletion;
- A40:
- represents Ile, or a deletion;
- A41:
- represents Thr, or a deletion;
- and
- A42:
- represents Gln, or a deletion.
62 more elements
A GIP receptor agonist peptide represented by formula (II):
- P1-Tyr-A2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-A13-A14-Asp-A16-A17-A18-A19-A20-A21-Phe-Val-A24-Trp-Leu-Leu-Ala-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-A40-A41-A42-P2, or a pharmaceutically acceptable salt thereof, wherein:
- P1 represents a group represented by formula
- —RA1,
- —CO—RA1,
- —CO—ORA1,
- —CO—CORA1,
- —SO—RA1,
- —SO2—RA1,
- —SO2—ORA1,
- —CO—NRA2RA3
- —SO2—NRA2RA3, or
- —C(═NRA1)—NRA2RA3
- wherein RA1, RA2, and RA3 each independently represent a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;
- P2 represents —NH2 or —OH;
- A2:
- represents Aib, D-Ala, or Gly;
- A13:
- represents Aib, or Ala;
- A14:
- represents Leu, Aib, Ile, Nle, or Lys(R);
- A16:
- represents Arg, Ser, or Lys;
- A17:
- represents Aib, Ala, Ile, or Lys(R);
- A18:
- represents Ala, His, or Lys(R);
- A19:
- represents Gln or Ala;
- A20:
- represents Aib, Gln, Arg, or Ala;
- A21:
- represents Asp, Asn, or Lys(R);
- A24:
- represents Asn, Gln, or Glu;
- A29:
- represents Gln, or Lys(R)
- A30:
- represents Arg, Lys, Ser, Gln, or Lys(R);
- A31:
- represents Gly, Pro, or a deletion;
- A32:
- represents Ser, Lys, Pro, Gly, or a deletion;
- A33:
- represents Ser, Lys, Gly, or a deletion;
- A34:
- represents Gly, Asn, or a deletion;
- A35:
- represents Ala, Asp, Ser, Asn, or a deletion;
- A36:
- represents Pro, Trp, or a deletion;
- A37:
- represents Pro, Lys, or a deletion;
- A38:
- represents Pro, His, or a deletion;
- A39:
- represents Ser, Asn, or a deletion;
- A40:
- represents Ile, or a deletion;
- A41:
- represents Thr, or a deletion;
- A42:
- represents Gln, or a deletion.
- wherein in the residue Lys(R), the (R) portion represents X-L-, wherein L represents a linker, and is selected from the following group consisting of 2OEGgEgE, OEGgEgE, 2OEGgE, 3OEGgEgE, G5gEgE, 2OEGgEgEgE, 2OEG and G5gEgE;
- and X represents a lipid.
61 more elements
A GIP receptor agonist peptide represented by formula (IV):
- P1-Tyr-Aib-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-A13-A14-Asp-A16-A17-A18-A19-A20-A21-Phe-Val-A24-Trp-Leu-Leu-Ala-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-P2, or a pharmaceutically acceptable salt thereof, wherein:
- P1 represents H or C1-6 alkyl;
- P2 represents —NH2 or —OH;
- A13:
- represents Aib, Ala, or Lys;
- A14:
- represents Leu, Aib, Lys, or Lys(R);
- A16:
- represents Arg, Ser, or Lys;
- A17:
- represents Aib, Ala, Ile, Glu, Lys, or Lys(R);
- A18:
- represents Ala, His, Glu, Lys, or Lys(R);
- A19:
- represents Gln or Ala;
- A20:
- represents Aib, Ala, Gln, Arg, or Lys;
- A21:
- represents Asp, Asn, Lys, or Lys(R);
- A24:
- represents Asn or Glu;
- A29:
- represents Gln, Lys, or Lys(R);
- A30:
- represents Arg, Ser, Gln, Lys, Lys(Ac), or Lys(R);
- A31:
- represents Gly, Pro, or a deletion;
- A32:
- represents Ser, Gly, or a deletion;
- A33:
- represents Ser, Gly, or a deletion;
- A34:
- represents Gly or a deletion;
- A35:
- represents Ala, Ser, or a deletion;
- A36:
- represents Pro or a deletion;
- A37:
- represents Pro or a deletion;
- A38:
- represents Pro or a deletion;
- and
- A39:
- represents Ser or a deletion;
- wherein in the residue Lys(R), the (R) portion represents X-L-, wherein L represents a linker and is selected from the group consisting of 2OEGgE, 2OEGgEgE, G4gE, GGGGG, G5gE, G5gEgE, G6, gEgEgE, OEGgEgE, OEGgEOEGgE, GGPAPAP, and GGPAPAPgE;
- and X represents C17-C22 monoacid or C17-C22 diacid.
43 more elements
Dependencies are inferred from the claim text.