Melanocortin 1 receptor ligands and methods of use

Patent metadata

Field	Value
Publication number	US-11230568-B2
Application number	US-201916450382-A
Country	US
Kind code	B2
Filing date	Jun 24, 2019
Priority date	May 17, 2011
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

First claim

We claim:

1. A method of treating melanoma in a human or non-human animal subject, comprising administering an MC1R-targeted agent to the subject, wherein the MC1R-targeted agent comprises a MC1R peptide ligand and a moiety, wherein the moiety comprises an anti-cancer agent, and wherein the MC1R peptide ligand and the moiety are covalently linked by a reaction product of a first functionality coupled to the MC1R peptide ligand and a complementary second functionality coupled to the moiety, wherein the MC1R peptide ligand comprises:

(SEQ ID NO: 3)

4-phenylbutyryl-His-DPhe-Arg-Trp-Gly-Lys

(hex-5-ynoyl)-NH 2 ;

or

(SEQ ID NO: 4)

H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-

Arg-DTrp-Asp-Arg-Phe-Gly-NH 2 ;

or 

(SEQ ID NO: 5)

H-Lys(hex-5-ynoyl)Tyr-Val-Nle-Gly-His-DNal(2′)- 

Arg-DPhe-Asp-Arg-Phe-Gly-NH 2 ; 

or

(SEQ ID NO: 6)

4-phenylbutyryl-His-DPhe-Arg-Trp,

and
a functional group coupled to the C-terminus of the MC1R peptide ligand.

2. The method of claim 1 , wherein the MC1R peptide ligand comprises 4-phenylbutyryl-Hi s-DPhe-Arg-Trp-Gly-Lys(hex-5-ynoyl)-NH 2 (SEQ ID NO:3).

3. The method of claim 1 , wherein the MC1R peptide ligand comprises H-Lys(hex-5-ynoyl)-Tyr-Val-Nle-Gly-His-DNal(2′)-Arg-DTrp-Asp-Arg-Phe-Gly-NH 2 (SEQ ID NO:4).

4. The method of claim 1 , wherein the MC1R peptide ligand comprises H-Lys(hex-5-ynoyl)Tyr-Val-Nle-Gly-His-DNal(2′)-Arg-DPhe-Asp-Arg-Phe-Gly-NH 2 (SEQ ID NO:5).

5. The method of claim 1 , wherein the MC1R peptide ligand comprises 4-phenylbutyryl-His-DPhe-Arg-Trp (SEQ ID NO:6).

6. The method of claim 1 , wherein the subject is human.

7. The method of claim 1 , wherein the subject is a non-human animal.

8. The method of claim 1 , wherein the melanoma is metastatic melanoma.

9. The method of claim 1 , wherein the anti-cancer agent kills melanoma cells or inhibits growth of melanoma cells.

10. The method of claim 1 , wherein the anti-cancer agent is a chemotherapeutic agent.

11. The method of claim 1 , wherein the anti-cancer agent is a cytotoxic agent.

12. The method of claim 1 , wherein the anti-cancer agent is a taxane.

13. The method of claim 1 , wherein the anti-cancer agent is one or more selected from among melphalan, ifosfamide, dacarbazine, paclitaxel, and vincristine.

14. The method of claim 1 , wherein the MC1R-targeted agent is administered systemically.

15. The method of claim 1 , wherein the MC1R-targeted agent is administered locally at a site of the melanoma.

16. The method of claim 1 , wherein the MC1R-targeted agent is administered orally or intravenously.

17. The method of claim 1 , wherein the MC1R-targeted agent is in a pharmaceutical composition comprising the MC1R-targeted agent and a pharmaceutically acceptable carrier, and wherein the pharmaceutical composition is administered to the subject.

18. The method of claim 17 , wherein the pharmaceutical composition is administered by intratumoral injection.

Assignees

• H Lee Moffitt Cancer Ct & Res
• Intezyne Tech Inc
• Univ Arizona
• Board Of Regents Univ Of Texas System
• Board Of Regents Untversity Of Texas System

Inventors

• Gillies Robert J
• Morse David L
• Barkey Natalie M
• Sill Kevin N
• Vagner Josef
• Tafreshi Narges K
• Sessler Jonathan L
• Preihs Christian
• Hruby Victor J

Classifications

• A61K47/6907

  the form being a microemulsion, nanoemulsion or micelle · CPC title

• A61K49/1809

  Micelles, e.g. phospholipidic or polymeric micelles · CPC title

• A61K49/101

  the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals · CPC title

• C07K14/68

  Melanocyte-stimulating hormone [MSH] · CPC title

• A61K38/34

  Melanocyte stimulating hormone [MSH], e.g. alpha- or beta-melanotropin · CPC title