TPC2-A1-N

SKU: orb1693428

Description

TPC2-A1-N is a cell-permeable, subtype-selective agonist for endogenous two-pore channel 2 (TPC2). It facilitates the study of TPC2 function in intact cells by inducing a time-dependent, moderate alkalinization of lysosomal pH. This tool is applicable for lysosomal physiology and channel pharmacology research in both in vitro and in vivo models.

Research Area

Metabolism Research, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 136186-07-7
• MW: 401.17
• Purity: 99.86% (May vary between batches)
• Formula: C₁₇H₉Cl₂F₃N₂O₂
• SMILES: O\C(=C(\C#N)C(=O)Nc1ccc(cc1)C(F)(F)F)c1cc(Cl)cc(Cl)c1
• Target: Calcium Channel
• Solubility: DMSO:200 mg/mL (498.54 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (12.46 mM)

Bioactivity

• Target IC50:
  Ca2+ current response from TPC2:10.5 μM (EC50)|Ca2+:10.5 μM (EC50)
• In Vitro:
  Two-pore channels (TPC1-3) are ancient members of the voltage-gated ion channel superfamily, expressed throughout the endo-lysosomal system, and regulate the trafficking of various cargoes. TPC2 mediates different physiological and potentially pathophysiological effects depending on its activation, with its ion selectivity being agonist-dependent. TPC2 uniquely conducts different ions in response to different activating ligands. TPC2-A1-N (10 μM) reproducibly evokes Ca2+ signals, achieving its plateau faster than TPC2-A1-P, with an EC50 of 7.8 μM in cells stably expressing TPC2L11A/L12A. TPC2-A1-N (10 μM) induces Ca2+ influx through TPC2 in TPC2L11A/L12A-expressing cells but not in TPC2L11A/L12A/L265P-expressing cells. TPC2-A1-N responses can be selectively blocked by Tetrandrine, Raloxifene, and Fluphenazine by removing extracellular Ca2+. In endo-lysosomal patch-clamp experiments, TPC2-A1-N (30 μM) elicits Na+ currents in vacuolin-enlarged endo-lysosomes isolated from HEK293 cells transiently expressing human TPC2 (hTPC2) but not in cells expressing TPC1. Furthermore, TPC2-A1-N (30 μM) induces larger currents in endo-lysosomes from cells expressing the gain-of-function TPC2M484L variant compared to the wild-type isoform, with an EC50 of 0.6 μM for TPC2-A1-N.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TPC2 A1 N, TPC2A1N, TPC-2-A1-N, TPC2-A1-N, TPC2, CalciumChannel, Calcium Channel

Quick Database Links

Gene Symbol

Calcium Channel