2. Academic Validation
  3. Discovery of Nonpungent Transient Receptor Potential Vanilloid 1 (TRPV1) Agonist as Strong Topical Analgesic

Discovery of Nonpungent Transient Receptor Potential Vanilloid 1 (TRPV1) Agonist as Strong Topical Analgesic

  • J Med Chem. 2020 Jan 9;63(1):418-424. doi: 10.1021/acs.jmedchem.9b01046.
Jihyae Ann 1,  Ho Shin Kim 1,  Shivaji A Thorat 1,  Hee Kim 2,  Hee-Jin Ha 2,  Kwanghyun Choi 2,  Young-Ho Kim 2,  Minseok Kim 3,  Sun Wook Hwang 3,  Larry V Pearce 4,  Timothy E Esch 4,  Noe A Turcios 4,  Peter M Blumberg 4,  Jeewoo Lee 1
Affiliations

Affiliations

  • 1 Laboratory of Medicinal Chemistry, College of Pharmacy , Seoul National University , 1 Gwanak-ro , Gwanak-gu, Seoul 08826 , Republic of Korea.
  • 2 Medifron DBT , Sandanro 349 , Danwon-gu, Ansan-si , Gyeonggi-do 15426 , Republic of Korea.
  • 3 Department of Biomedical Sciences and Department of Physiology , Korea University College of Medicine , Seoul 02841 , Republic of Korea.
  • 4 Laboratory of Cancer Biology and Genetics, Center for Cancer Research , National Cancer Institute, NIH , Bethesda , Maryland 20892-4255 , United States.
PMID: 31702924 DOI: 10.1021/acs.jmedchem.9b01046
Abstract

Paradoxically, some TRPV1 agonists are, at the organismal level, both nonpungent and clinically useful as topical analgesics. Here, we describe the scaled-up synthesis and characterization in mouse models of a novel, nonpungent vanilloid. Potent analgesic activity was observed in models of neuropathic pain, and the compound blocked capsaicin induced allodynia, showing dermal accumulation with little transdermal absorption. Finally, it displayed much weaker systemic toxicity compared to capsaicin and was negative in assays of genotoxicity.

Figures
Products