IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jul 25

PMID 35875081

Authors

Hongmei Liu

Huan Gao

Cheng Chen

Wenyu Jia

Delong Xu

Guan Jiang

Affiliations

Soon will be listed here.

Abstract

In this study, we synthesized a molecule GA-1MT (GM) composed of indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-d-tryptophan, 1MT) called NLG8189 and gallic acid (GA) and verified its therapeutic effect on B16F10 melanoma cells and an orthotopic tumor-bearing mouse model. The synthesized molecule GM was analyzed by H NMR and mass spectrometry (MS). In addition, we confirmed that GM could mediate the immune response in the B16F10 cell tumor model by flow cytometry and immunofluorescence. The synthesized GM molecule could increase the solubility of 1MT to enhance the drug efficacy and lower costs. Moreover, GM could inhibit melanoma growth by combining 1MT and GA. experiments showed that GM could effectively inhibit the expression of tyrosinase, regulate the proportion of CD4 T cells, CD8 T cells, and regulatory T cells (T cells) in tumors, and significantly suppress melanoma growth. The newly synthesized drug GM could more effectively inhibit melanoma than GA and 1MT alone or in combination.

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