Conjugation of MCR1 ligand with cytotoxic drugs for treating skin cancer
AssigneeArizona Board of Regents on Behalf of the University of Arizona
InventorsMinying Cai, Victor J. Hruby, Yang Zhou
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Abstract
Ligand-drug conjugates for targeted melanoma therapies are disclosed herein. A ligand is conjugated to a cytotoxic cancer drug through a cleavage linker. The ligand can bind to an overexpressed receptor on a cancer cell, resulting in selectivity. This allows the drug to enter a cancer cell selectively and release the drug within that specific cancer cell. Such therapies provide selectivity to melanoma through a ligand that targets the MC1R receptor, which is highly expressed in 80% of malignant melanomas. The ligand-drug conjugates can be used to deliver a wide range of cytotoxic cancer drugs selective to melanoma cells which may solve the drug resistance problem of melanoma in current therapies.
Claims16
A pharmaceutical composition comprising a ligand-drug conjugate comprising a peptide ligand bound to a drug moiety, wherein the ligand-drug conjugate is according to the formula:
- L-A-B-D, wherein L is the peptide ligand, A is a spacer derived from aminohexanoic acid, B is a cleavable linker, and D is the drug moiety, wherein the peptide ligand is according to the formula:
- Ac-Nle-c[Asp-His-Taa-Arg-Trp-Lys]-NH2 (SEQ ID NO:
- 89), or is a derivative that has at least 50% homology to SEQ ID NO:
- 89, wherein Taa is DPhe or DNal(2′).
A pharmaceutical composition comprising a ligand-drug conjugate, wherein the ligand-drug conjugate is according to the following:
- wherein MT-II is Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 (SEQ ID NO:
- 4).
A pharmaceutical composition comprising a ligand-drug conjugate comprising a peptide ligand bound to a drug moiety, wherein the ligand-drug conjugate is according to the formula:
- L-A-B-D, wherein L is the peptide ligand, A is a spacer, B is a cleavable linker, and D is the drug moiety, wherein the peptide ligand is according to the formula:
- Ac-Nle-c[Asp-His-Taa-Arg-Trp-Lys]-NH2 (SEQ ID NO:
- 89), or is a derivative that has at least 50% homology to SEQ ID NO:
- 89, wherein Taa is DPhe or DNal(2′), wherein the peptide ligand has at least one backbone residue that is N-methylated.
Dependencies are inferred from the claim text.