2. Academic Validation
  3. Discovery of O-alkylated derivative of piperine as Nav1.7 channel inhibitor for the treatment of pain

Discovery of O-alkylated derivative of piperine as Nav1.7 channel inhibitor for the treatment of pain

  • Bioorg Med Chem Lett. 2026 Feb 1:131:130461. doi: 10.1016/j.bmcl.2025.130461.
Vikrant Nawal Vikram 1,  Madhavi Ranawat 2,  Aditya Singh 3,  Shiv Kumar 1,  Ashutosh Sharma 2,  Shivani Yadav 2,  Vikash Kumar 4,  Aravind Singh Kshatri 5,  Tadigoppula Narender 6
Affiliations

Affiliations

  • 1 Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 2 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Neuroscience and Ageing Biology Division, CSIR- Central Drug Research Institute, Lucknow 226031, India.
  • 3 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 4 Neuroscience and Ageing Biology Division, CSIR- Central Drug Research Institute, Lucknow 226031, India.
  • 5 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Neuroscience and Ageing Biology Division, CSIR- Central Drug Research Institute, Lucknow 226031, India. Electronic address: [email protected].
  • 6 Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: [email protected].
PMID: 41197882 DOI: 10.1016/j.bmcl.2025.130461
Abstract

Millions of people are being affected by chronic pain, and it is insufficiently addressed by the current classes of analgesics. Nav1.7 channels have emerged as promising targets in this pain context since their systemic inhibition can cancel pain perception altogether. In this work, we report a novel, O-alkylated piperine derivative 3ag as an inhibitor of Nav1.7 channels with an IC50 of 3.10 μM. Furthermore, this molecule displayed an oral analgesic efficacy in a CFA inflammatory pain model at 10 mg/kg. Based on our findings, this molecule could be used as a starting point for the development of new Nav1.7-specific blockers for anti-nociception.

Keywords

Electrophysiology; Natural products; Nav1.7 channels; Pain; Piperine; Screening.

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