| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
EC50: 10.5 μM (TPC2)[2]
The primary target of TPC2-A1-P is the two-pore channel 2 (TPC2), an endolysosomal ion channel that plays a role in intracellular calcium and sodium signaling. TPC2-A1-P acts as a potent agonist, mimicking the physiological activation of TPC2 by NAADP and PI(3,5)P2. By activating TPC2, the compound modulates endolysosomal signaling pathways. It has an EC50 of 10.5 μM for TPC2 activation and is a valuable tool for studying the role of TPC2 in various cellular processes, including neurodegeneration and lysosomal storage disorders. |
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| ln Vitro |
Ancient members of the voltage-gated ion channel superfamily are known as two-pore channels (TPC1-3). TPCs govern the trafficking of many payloads and are expressed throughout the endo-lysosomal system[1]. Depending on how it is triggered, TPC2 can mediate various physiological and potentially pathological effects. TPC2's ion selectivity is agonist-dependent rather than fixed. One special type of ion channel that responds to various activating ligands by conducting distinct ions is TPC2[1]. Does TPC2-A1- P (10 μM) consistently elicit Ca2+?signals, and compared to TPC2-A1-N, the TPC2-A1-P response reaches its plateau more slowly. The 50th EC?In a cell line that consistently expresses TPC2L11A/L12A, the entire concentration-effect relationships for the plateau response are 10.5 μM for TPC2-A1-P. TPC2-A1-P generates Ca2+ at 10-30 μM?signals in Hela cells that express TPC2 when extracellular Ca2+ is present but not absent. In contrast to TPC2-A1-N, the reactions are smaller and more gradual, which is in line with the outcomes seen in cells that express TPC2L11A/L12A stable. Can't TPC2-A1-P induce Ca2+?signals in cells that do not elicit Ca2+ influx and express "pore-dead" TPC2L11A/L12A/L265P?signals were redirected to the plasma membrane (TRPML1ΔNC) in cells expressing human TRPML1[1]. Endo-lysosomes isolated from cells expressing TPC2 and TPC2M484L exhibit currents evoked by TPC2-A1-P (10 μM) in endo-lysosomal patch-clamp experiments. The currents evoked by TPC2-A1-P are significantly larger than those evoked by TPC2-A1-N in both wild-type and gain-of-function variant, and exhibit an EC50?0.6 μM was the result for TPC2-A1 -P[1].
In vitro, TPC2-A1-P is a potent agonist of TPC2 with an EC50 of 10.5 μM. It activates TPC2 by mimicking the physiological actions of NAADP and PI(3,5)P2. Compared to TPC2-A1-N, TPC2-A1-P has a higher capacity to induce Na+ activation. The compound is membrane-permeable, allowing it to be used in intact cell assays to study TPC2 function. TPC2-A1-P is soluble in DMSO at 50 mg/mL (108.63 mM) and is available with a purity of ≥99%. |
| ln Vivo |
In vivo, TPC2-A1-P has potential applications in the study of neurodegenerative lysosomal storage disorders and other diseases involving endolysosomal dysfunction. By activating TPC2, the compound can modulate calcium and sodium signaling pathways that are critical for lysosomal function and cellular homeostasis. However, detailed in vivo efficacy and safety data are not extensively reported in the available literature, and its use is primarily limited to preclinical research settings. Further studies are needed to fully characterize its in vivo effects and therapeutic potential.
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| Enzyme Assay |
In vitro assays for TPC2-A1-P typically involve measuring its activation of TPC2 channels using electrophysiological techniques such as patch-clamp recording in cells expressing recombinant TPC2 channels. The compound is applied to the cells at varying concentrations, and the resulting changes in ion current are measured. The EC50 of 10.5 μM is determined by fitting concentration-response curves. Fluorescent-based assays using calcium or sodium indicators can also be used to measure TPC2-mediated ion flux in response to compound treatment.
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| Cell Assay |
Cellular assays for TPC2-A1-P typically use cell lines expressing endogenous or recombinant TPC2 channels. Cells are treated with the compound (typically at concentrations around the EC50 of 10.5 μM), and the effects on TPC2-mediated ion flux are measured using fluorescent indicators for calcium or sodium. The compound's ability to activate TPC2 and its differential effects compared to TPC2-A1-N can be assessed. These assays are used to study the role of TPC2 in endolysosomal signaling, lysosomal function, and cellular homeostasis.
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| Animal Protocol |
In vivo animal studies for TPC2-A1-P would likely involve the administration of the compound to animal models of neurodegenerative lysosomal storage disorders or other diseases involving TPC2 dysfunction. The compound could be administered via intravenous injection or other routes appropriate for its pharmacokinetic properties. Endpoints would depend on the specific disease model and could include measurements of lysosomal function, neuronal survival, and behavioral outcomes. However, specific in vivo study protocols for TPC2-A1-P are not detailed in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for TPC2-A1-P are not extensively reported in the available literature. The compound has a molecular weight of 460.28 g/mol and is membrane-permeable. It is soluble in DMSO at 50 mg/mL and is available with a purity of ≥99%. For research purposes, the compound is typically stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years. Detailed parameters such as half-life, volume of distribution, and bioavailability are not publicly available and would need to be determined experimentally.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for TPC2-A1-P in the available literature. As a research chemical intended for laboratory use only, it should be handled with standard safety precautions for handling chemical reagents. The compound is not approved for human therapeutic use. Researchers should consult the material safety data sheet (MSDS) for detailed safety and handling information. Any potential toxicity would need to be assessed through formal toxicological studies if the compound were to be developed further.
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| References | |
| Additional Infomation |
TPC2-A1-P is a membrane-permeable, potent agonist of the two-pore channel 2 (TPC2) with an EC50 of 10.5 μM. It has a molecular formula of C20H21BrF3NO3 and a molecular weight of 460.28 g/mol. TPC2-A1-P mimics the activation of TPC2 by NAADP and PI(3,5)P2 and has a higher capacity to induce Na+ activation compared to TPC2-A1-N. The compound is used to study TPC2 function in endolysosomal signaling and neurodegenerative disorders and is soluble in DMSO.
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| Molecular Formula |
C20H21BRF3NO3
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|---|---|
| Molecular Weight |
460.284855604172
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| Exact Mass |
459.065
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| CAS # |
2804595-86-4
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| PubChem CID |
154730265
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| Appearance |
White to light yellow solid powder
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| LogP |
6.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
541
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(N1CC2CCCCC2)C3=C(C=CC(=C3)Br)OC(F)(F)F)C(=O)O
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| InChi Key |
INDFMVADKKBSSU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21BrF3NO3/c1-12-15(19(26)27)10-17(25(12)11-13-5-3-2-4-6-13)16-9-14(21)7-8-18(16)28-20(22,23)24/h7-10,13H,2-6,11H2,1H3,(H,26,27)
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| Chemical Name |
5-[5-bromo-2-(trifluoromethoxy)phenyl]-1-(cyclohexylmethyl)-2-methylpyrrole-3-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50 mg/mL (108.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1726 mL | 10.8630 mL | 21.7259 mL | |
| 5 mM | 0.4345 mL | 2.1726 mL | 4.3452 mL | |
| 10 mM | 0.2173 mL | 1.0863 mL | 2.1726 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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