Lipoyl-Homotaurine Derivative (ADM_12) Reverts Oxaliplatin-Induced Neuropathy and Reduces Cancer Cells Malignancy by Inhibiting Carbonic Anhydrase IX (CAIX)

J Med Chem. 2017 Nov 9;60(21):9003-9011. doi: 10.1021/acs.jmedchem.7b01237. Epub 2017 Oct 27.

Abstract

Oxaliplatin (OXA) is a valuable and largely used cancer drug which induces a serious and intractable neuropathy. The lipoyl-homotaurine derivative (ADM_12) reverts in vivo OXA-induced neuropathy, and it is an effective antagonist of the nociceptive sensor channel TRPA1. Unprecedentedly, this safe analgesic showed a synergy with OXA in vitro and proved to inhibit CA IX, a relevant therapeutic target, clearly interfering with pancreatic cancer cells' aggressiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / toxicity
  • Carbonic Anhydrase IX / antagonists & inhibitors*
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Cell Line, Tumor
  • Drug Synergism
  • Humans
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Organoplatinum Compounds / therapeutic use
  • Organoplatinum Compounds / toxicity*
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / pathology
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / drug therapy*
  • TRPA1 Cation Channel / antagonists & inhibitors
  • Taurine / analogs & derivatives*
  • Taurine / chemistry
  • Taurine / pharmacology

Substances

  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Organoplatinum Compounds
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Oxaliplatin
  • Taurine
  • tramiprosate
  • Carbonic Anhydrase IX