TPC2-A1-N

Research use only, not for human use.

TPC2-A1-N is a novel lipophilic, membrane-permeable subtype-selective TPC2 small molecule agonist that activates endogenous TPC2 to moderately increase lysosomal pH in untransfected cells in a time-dependent manner, and can be used to assay the differential function of TPC2 channels in intact cells.

TPC2-A1-N is a powerful and Ca2+-permeable agonist of?two pore?channel?2?(TPC2), which plays its role by mimicking the physiological actions?of?NAADP. TPC2-A1-P reproducibly?evokes significant Ca2+ responses from TPC2 (EC50=7.8 μM), and the effect can be blocked by several TPC blockers. TPC2-A1-N can be used to probe different functions of TPC2 channels in intact cells.

Two-pore channels (TPC1-3) are ancient members of the voltage-gated ion channel superfamily. TPCs are expressed throughout the endo-lysosomal system and regulates the trafficking of various cargoes.TPC2 can mediate different physiological and possibly pathophysiological effects depending on how it is activated.?The?ion selectivity of TPC2 is not fixed but rather agonist-dependent. TPC2 is a unique example of an ion channel that conducts different ions in response to different activating ligands.TPC2-A1-N (10 μM) reproducibly evokes Ca2+?signals, and TPC2-A1-N response reachs its plateau faster than TPC2-A1-P. The EC50 in full concentration-effect relationships for the plateau response is 7.8 μM for TPC2-A1-N in a cell line stably expressing TPC2L11A/L12A.TPC2-A1-N (10 μM) evokes Ca2+?influx through the TPC2 pore evokes Ca2+?signals in cells expressing TPC2L11A/L12A?but not TPC2L11A/L12A/L265P. Additionally, the responses to TPC2-A1-N can be selectively blocked by the identified TPC2 blockers Tetrandrine (HY-13764, Tet), Raloxifene (HY-13738, Ral), and Fluphenazine (HY-A0081, Flu) by removal of extracellular Ca2+.In endo-lysosomal patch-clamp experiments, TPC2-A1-N (30 μM) elicits currents using Na+?as the major permeantion, in vacuolin-enlarged endo-lysosomes isolated from isolated from HEK293 cells transiently expressing human TPC2 (hTPC2) but not in cells expressing TPC1.In endo-lysosomal patch-clamp experiments, TPC2-A1-N (30 μM) induces larger currents in endo-lysosomes isolated from cells expressing a gain-of-function variant of TPC2 (TPC2M484L) compared to the wild-type isoform, and exhibits an EC50 value of 0.6 μM for TPC2-A1-N.

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GPCR/G Protein

Calcium Channel

Calcium Channel

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136186-07-7

401.17

C17H9Cl2F3N2O2

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (623.18 mM; Ultrasonic )

O\C(=C(\C#N)C(=O)Nc1ccc(cc1)C(F)(F)F)c1cc(Cl)cc(Cl)c1

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(-20℃)

With Ice Pack

≥ 2 years