TPC2-A1-P

Research use only, not for human use.

TPC2-A1-P is a membrane-permeable two-pore channel 2 (TPC2) agonist that differentially activates two-pore channel 2 (TPC2) and mimics the activation of TPC2 with NAADP and PIP(2). TPC2-A1-P can be used to study neurodegenerative lysosomal storage diseases.

TPC2-A1-P is a powerful and membrane permeable agonist of?two pore?channel?2?(TPC2) with an EC50 of 10.5 μM. TPC2-A1-P plays its role by mimicking the physiological actions?of?PI(3,5)P2. TPC2-A1-P also shows higher potency to induce Na2+ mobilisation from TPC2 than TPC-A1-N (HY-131614). TPC2-A1-P 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-P (10 μM) reproducibly evokes Ca2+signals, and TPC2-A1-P response reachs its plateau slower than TPC2-A1-N (HY-131614). The EC50?in full concentration-effect relationships for the plateau response is 10.5 μM for TPC2-A1-P in a cell line stably expressing TPC2L11A/L12A.TPC2-A1-P (10-30 μM) induces Ca2+signals in Hela cells expressing TPC2 in the presence but not absence of extracellular Ca2+. However, the responses are smaller and delayed compared to TPC2-A1-N (HY-131614), consistent with the results obtained in cells stably expressing TPC2L11A/L12A. TPC2-A1-P fails to induce Ca2+signals in cells expressing ‘pore-dead’ TPC2L11A/L12A/L265P and also fails to evoke Ca2+ signals in cells expressing human TRPML1 re-routed to the plasma membrane (TRPML1ΔNC).In endo-lysosomal patch-clamp experiments, TPC2-A1-P (10 μM) evokes currents in endo-lysosomes isolated from cells expressing TPC2 and TPC2M484L, the currents evoked by TPC2-A1-P are significantly larger than those evoked by TPC2-A1-N (HY-131614) in both wild-type and gain-of-function variant,and exhibits an EC50 value of 0.6 μM for TPC2-A1-P.

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GPCR/G Protein

Calcium Channel

Calcium Channel

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2804595-86-4

460.29

C20H21BrF3NO3

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (108.63 mM; Ultrasonic )

O=C(O)C=1C=C(C=2C=C(Br)C=CC2OC(F)(F)F)N(C1C)CC3CCCCC3

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(-20℃)

With Ice Pack

≥ 2 years