PSMA-targeted NIR dyes and their uses
AssigneeOn Target Laboratories, LLC
InventorsSumith A. Kularatne, Philip S. Low, Pravin Gagare
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.
Claims20
A compound having the formula:
- B-X-Y-Z,
- wherein
- B comprises a compound capable of binding to prostate specific membrane antigen (PSMA),
- X is selected from the group consisting of polyethylene glycol (PEG), N-amino-dPEG2-acid and polyethylene amine (PEA),
- Y comprises at least one amino acid, or derivative thereof, and
- Z comprises a near-infra red (NIR) dye.
A compound having the formula:
- B-X-Y-Z,
- wherein
- B comprises DUPA or a derivative thereof;
- X is selected from the group consisting of, PEG, N-amino-dPEG2-acid, and PEA;
- Y is selected from the group consisting of phenylalanine-tyrosine, histidine-tyrosine, phenylalanine-arginine-tyrosine, and histidine-tyrosine;
- and Z comprises S0456.
A compound having the structural formula:
- or a pharmaceutically acceptable salt thereof, or isotopes thereof, wherein:
- R1 represents a hydrogen or SO3H;
- R2 represents a hydrogen, or CH3, or C3H6SO3−, or C3H6SO3H or C4H8SO3−, or C4H8SO3H or C3H6N+(CH3)3;
- R3, and R5 each represents a carbon, optionally one or more sharing bonds, or oxygen, or sulfur, or nitrogen R4 represents a carbon with optionally one or more sharing bonds;
- R6 represents nitrogen, oxygen, or sulfur or no atom (direct C—C bond between aromatic ring and vinyl ring);
- R7 is optional and when present represents electron donating aromatic substitution group;
- R8 is optional and when present represents linkers with aromatic amino acids such as Phe, Trp, His, Tyr, or derivative of them, and/or cationic amino acids such Arg, Lys, or derivative of them, and/or anionic amino acids such as Asp, Glu or derivative of them, and/or unnatural amino acids of aromatic/cationic/anionic acids or derivative;
- R9 represents a PEG, N-amino-dPEG2-acid, PEA, or derivative of them;
- R10 represents a CO2H, PO3H2, SO3H, CH2SO3H, CH2CONHCH2SO3H, CH2CONHCH2CH2SO3H;
- R11 represents CO2H, SO3H, CH2CONHCH2SO3H, CH2CONHCH2CH2SO3H;
- and
- R12 represents independently represents a hydrogen, a methyl group, CH2COOH, a CH2 and may optionally represent each a CH2 sharing a bond.
A compound having the formula:
- B-X-Y-Z,
- wherein
- B comprises a compound capable of binding to prostate specific membrane antigen (PSMA),
- X is selected from the group consisting of polyethylene glycol (PEG), N-amino-dPEG2-acid and polyethylene amine (PEA),
- Y comprises at least one amino acid or derivative thereof, wherein the amino acid derivative is a derivative of tyrosine selected from the group consisting of:
- or racemic mixtures thereof, and
- Z comprises a near-infra red (NIR) dye.
Dependencies are inferred from the claim text.