Synthesis and Agonistic Activity at the GPR35 of 5,6-Dihydroxyindole-2-carboxylic Acid Analogues

  • ACS Med Chem Lett. 2012 Jun 6;3(7):550-4. doi: 10.1021/ml300076u.
Huayun Deng  1 ,  Ye Fang  1
Affiliations
  • 1. Biochemical Technologies, Science and Technology Division, Corning Inc. , Corning, New York 14831, United States.
PMID: 24900508 DOI: 10.1021/ml300076u
Abstract

5,6-Dihydroxyindole-2-carboxylic acid (DHICA), an intermediate of melanin synthesis and an eumelanin building block, was recently discovered to be a GPR35 Agonist with moderate potency. Here, we report the synthesis and pharmacological characterization of a series of DHICA analogues against GPR35 using both label-free dynamic mass redistribution and Tango β-arrestin translocation assays. This led to identification of novel GPR35 agonists with improved potency and/or having biased agonism.

Keywords
5,6-dihydroxyindole-2-carboxylic acid; GPR35; biased agonism; melanin synthesis.
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