TRPM4 Inhibitor NBA

Novel specific TRPM4 inhibitor, blocking TRPM4 currents in HCT116 cells, reducing the viability of Colo205 cells. NBA is an ammonium salt form (more water soluble) of TRPM4-IN-2 (Free Acid).

Mechanism / Binding & SAR (Structure-Activity Relationships)

1. Binding Site / Mode of Inhibition

   • The precise binding site of NBA on TRPM4 has not yet been definitively mapped, although some recent work aims to identify it. PMC+1

   • One publication (“Identification of a binding site for small-molecule inhibitors …”) indicates that efforts are ongoing to pinpoint where anthranilic acid derivatives (like NBA) bind. 

   • Because NBA is an aryloxyacyl-anthranilic acid derivative, its structural features (a naphthoxy substituent, anthranilic acid core) potentially allow interaction with hydrophobic pockets near the transmembrane domain, though this is speculative. Frontiers+2chimia.ch+2
     
     

2. Potency & Selectivity Compared to Other Inhibitors

   • NBA has an IC₅₀ of ~0.16 µM for TRPM4 inhibition.

   • In comparative studies with other TRPM4 inhibitors (e.g. CBA, LBA), NBA tends to show greater potency (i.e. require lower concentration for inhibition). 

   • In colorectal cancer (CRC) cells (HCT116), NBA, CBA, and LBA were found to almost fully block TRPM4 currents (91.8–98.5%) in the low micromolar range; NBA was the most potent among them. MDPI+1

   • Some inhibition is non-reversible in CRC cells (i.e. washout does not fully restore the current), which suggests either very tight binding or possibly partial inactivation. MDPI
     
     

3. Functional Consequences of Inhibition / Downstream Effects

   • In CRC cell lines, inhibition of TRPM4 by NBA was associated with:

     • Slowed proliferation. MDPI

     • Alteration of cell cycle distribution (increased proportion in G1 phase) at higher doses (e.g. ~50 µM). MDPI

     • Reduced viability in a CRC line (Colo205) that expresses high levels of TRPM4. MDPI

   • However, in some prostate cancer (PCa) cell models (DU145, LNCaP), NBA (and related inhibitors) did not reliably change functional readouts (viability, migration) despite blocking current—presumably because inhibition was incomplete or because TRPM4-mediated current alone is not entirely determinative of those phenotypes in those contexts. ScienceDirect+3MDPI+3PMC+3
     
     

4. Functional / Bioactive Profile

   • Target: TRPM4 (Transient Receptor Potential Melastatin 4) channel

   • Action: Inhibitor — it blocks or suppresses TRPM4 activity

   • Potency: IC₅₀ ≈ 0.16 µM (i.e. fairly potent) 

   • In vitro evidence: At 50 µM, TRPM4-IN-2 can block ~88 ± 9% of endogenous TRPM4 currents in DU145 prostate cancer cells over a 0-500 s exposure period.

   • Research uses: It is used as a tool compound in studies of cancer (notably prostate cancer, colorectal cancer) to explore how TRPM4 influences tumor cell behavior.

0°C (short term), -20°C (long term), desiccated

TRPM4-IN-2 Ammonium Salt