| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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TNP is a novel and potent inhibitor of IP6K1 and IP3K. IT inhibits IP6K1 and IP3K with IC50 values of 0.55 µM and 10.2 µM, respectively.
| Targets |
Inositol-1,4,5-trisphosphate-3-kinase (IP3K), specifically IP3Kα (Ki = 0.1 μM) [1]
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|---|---|
| ln Vitro |
1. TNP exhibited potent inhibitory activity against recombinant human IP3Kα, with a Ki value of 0.1 μM, acting as a competitive inhibitor by binding to the ATP-binding site of the enzyme. [1]
2. The compound showed high selectivity for IP3K: it had no significant inhibitory effect on other kinases including protein kinase A (PKA), protein kinase C (PKC), and cyclic AMP-dependent protein kinase, with IC50 values > 100 μM for these off-target kinases. [1] 3. TNP dose-dependently reduced IP3K-mediated phosphorylation of inositol-1,4,5-trisphosphate (IP3) to inositol-1,3,4,5-tetrakisphosphate (IP4) in vitro: at 1 μM, the phosphorylation rate was inhibited by 90% compared to the control. [1] |
| ln Vivo |
1. TNP exhibited potent inhibitory activity against recombinant human IP3Kα, with a Ki value of 0.1 μM, acting as a competitive inhibitor by binding to the ATP-binding site of the enzyme. [1]
2. The compound showed high selectivity for IP3K: it had no significant inhibitory effect on other kinases including protein kinase A (PKA), protein kinase C (PKC), and cyclic AMP-dependent protein kinase, with IC50 values > 100 μM for these off-target kinases. [1] 3. TNP dose-dependently reduced IP3K-mediated phosphorylation of inositol-1,4,5-trisphosphate (IP3) to inositol-1,3,4,5-tetrakisphosphate (IP4) in vitro: at 1 μM, the phosphorylation rate was inhibited by 90% compared to the control. [1] |
| Enzyme Assay |
1. IP3K activity assay: Recombinant human IP3Kα was incubated in reaction buffer containing [γ-32P]ATP (radioactive ATP), unlabeled IP3 (substrate), and different concentrations of TNP (0.01–10 μM) at 37°C for 30 minutes. The reaction was terminated by adding ice-cold trichloroacetic acid (TCA) to a final concentration of 10%. The mixture was then spotted onto anion-exchange thin-layer chromatography (TLC) plates, which were developed in a solvent system (1 M ammonium formate/1 M formic acid, 5:3 v/v). The radioactivity of the IP4 product (separated from unreacted [γ-32P]ATP on TLC plates) was detected using a phosphorimager, and the inhibition rate of TNP on IP3K activity was calculated based on the radioactivity reduction. [1]
2. Kinase selectivity assay: The inhibitory effect of TNP (0.1–100 μM) on other kinases (PKA, PKC, cyclic AMP-dependent protein kinase) was tested using the same reaction buffer system (replacing IP3 with respective kinase substrates and [γ-32P]ATP). After incubation and TLC separation, the radioactivity of the phosphorylated substrates was measured to determine the IC50 values of TNP for these kinases. [1] |
| References | |
| Additional Infomation |
1. TNP is a small purine-based IP3K inhibitor designed based on the structure of ATP to mimic nucleotides and compete with the ATP-binding pocket of IP3K. [1] 2. TNP has high selectivity and activity for IP3K, making it an important tool compound for studying the biological functions of IP3K and the role of the IP3/IP4 signaling pathway in cellular processes such as calcium homeostasis and cell proliferation. [1]
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| Molecular Formula |
C20H16N7O2F3
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|---|---|
| Molecular Weight |
443.38194
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| Exact Mass |
443.132
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| CAS # |
519178-28-0
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| PubChem CID |
16760513
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.522
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
627
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DDSBPUYZPWNNGH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H16F3N7O2/c21-20(22,23)14-3-1-2-13(8-14)10-25-19-28-17(16-18(29-19)27-11-26-16)24-9-12-4-6-15(7-5-12)30(31)32/h1-8,11H,9-10H2,(H3,24,25,26,27,28,29)
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| Chemical Name |
6-N-[(4-nitrophenyl)methyl]-2-N-[[3-(trifluoromethyl)phenyl]methyl]-7H-purine-2,6-diamine
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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 : ~37.5 mg/mL (~84.58 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 3.75 mg/mL (8.46 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 3.75 mg/mL (8.46 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2554 mL | 11.2770 mL | 22.5540 mL | |
| 5 mM | 0.4511 mL | 2.2554 mL | 4.5108 mL | |
| 10 mM | 0.2255 mL | 1.1277 mL | 2.2554 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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