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Novel Small Molecule Probes for Metastatic Melanoma.

ABSTRACT: Actively targeting probe 1b, an unsymmetrical bivalent dipeptide mimic, selectively bound melanoma over healthy skin tissue in histological samples from patients and Sinclair swine. Modifications to 1b gave agents 2-4 that contain a near-IR aza-BODIPY fluor. Contrary to our expectations, symmetrical probe 3 gave the highest melanoma-to-healthy skin selectivity in histochemistry and experiments with live cells; this was surprising because 2, not 3, is unsymmetrical like the original lead 1. Optical imaging of 3 in a mouse melanoma model failed to show tumor accumulation in vivo, but the probe did selectively accumulate in the tumor (some in lung and less in the liver) as proven by analysis of the organs post mortem.

SUBMITTER: Kamkaew A

PROVIDER: S-EPMC5304293 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Novel Small Molecule Probes for Metastatic Melanoma.

Kamkaew Anyanee A Fu Nanyan N Cai Weibo W Burgess Kevin K

ACS medicinal chemistry letters 20161209 2

Actively targeting probe 1b, an unsymmetrical bivalent dipeptide mimic, selectively bound melanoma over healthy skin tissue in histological samples from patients and Sinclair swine. Modifications to 1b gave agents 2-4 that contain a near-IR aza-BODIPY fluor. Contrary to our expectations, symmetrical probe 3 gave the highest melanoma-to-healthy skin selectivity in histochemistry and experiments with live cells; this was surprising because 2, not 3, ...[more]

PMID: 28197308

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