TFPI inhibitors and methods of use
View Patent ↗The invention provides peptides that bind Tissue Factor Pathway Inhibitor (TFPI), including TFPI-inhibitory peptides, and compositions thereof. The peptides may be used to inhibit a TFPI, enhance thrombin formation in a clotting factor-deficient subject, increase blood clot formation in a subject, and/or treat a blood coagulation disorder in a subject.
1. A peptide comprising an amino acid sequence of at least 85% identity to the sequence of formula VII:
(SEQ ID NO: 1040)
Ac-FYYKWH[CGMRDMKGTMSC]AWVKF-NH2, (VII)
wherein the peptide forms a cyclic structure generated by a disulfide bond between cysteines at amino acid positions 7 and 18 of the amino acid sequence.
2. The peptide according to claim 1 , wherein the amino acid sequence identity is at least 90%.
3. The peptide according to claim 1 , wherein the peptide is conjugated to a polyethylene glycol (PEG) moiety.
4. A method for treating a blood coagulation disorder in a subject, the method comprising administering to the subject a peptide of claim 1 in an amount sufficient to treat the blood coagulation disorder in the subject.
5. A pharmaceutical compositing comprising a peptide as defined claim 1 and a pharmaceutical acceptable carrier.
6. The peptide according to claim 1 , wherein the amino acid sequence identity is at least 95%.
7. A peptide comprising an amino acid sequence of at least 85% identity to the sequence of Ac-SGASRYKWFCGMRDMKGTMSCVWVKFRYDTS-NH2 (SEQ ID NO: 1047).
8. The peptide according to claim 7 , wherein the amino acid sequence identity is at least 90%.
9. The peptide according to claim 7 , wherein the amino acid sequence identity is at least 95%.
10. A pharmaceutical compositing comprising a peptide as defined claim 7 and a pharmaceutical acceptable carrier.