| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
UCL-TRO-1938 specifically targets the phosphatidylinositol 3-kinase alpha (PI3Kα) isoform. It functions as an allosteric activator, meaning it binds to a site distinct from the active site to induce a conformational change that enhances the enzyme's catalytic activity. This activation leads to the stimulation of downstream signaling pathways, including the phosphorylation of AKT (pAKT(S473)), which are critical for cell growth, survival, and metabolism. Unlike inhibitors, this compound is used to study the effects of heightened PI3K signaling.
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| ln Vitro |
In vitro studies have demonstrated that UCL-TRO-1938 activates PI3Kα with an EC50 of approximately 60 µM based on lipid kinase activity. In PI3Kα-WT mouse embryonic fibroblasts (MEFs), treatment with UCL-TRO-1938 for 24 hours increases metabolic activity with an EC50 of about 0.5 µM. This effect is PI3Kα-dependent, as it is not observed in PI3Kα-KO MEFs. However, at concentrations greater than 7.5 µM, ATP levels decline in both WT and KO MEFs, indicating potential off-target effects at higher doses. The compound also induces cell proliferation.
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| ln Vivo |
In vivo, UCL-TRO-1938 has shown significant cardioprotective effects in mouse models of ischemia-reperfusion injury (IRI). In male C57/BL6 mice, the compound was administered at a dose of 10 mg/kg, dissolved in DMSO. This treatment resulted in a pronounced cardioprotective effect, which was accompanied by elevated levels of pAKT(S473) in cardiac tissue, confirming target engagement and pathway activation in the heart. The compound's ability to enhance nerve regeneration following nerve crush has also been observed, supporting its potential in neuroregenerative applications.
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| Enzyme Assay |
Cell-free assays for UCL-TRO-1938 typically involve measuring its ability to directly activate PI3Kα lipid kinase activity in vitro. The compound's EC50 of approximately 60 µM is determined using biochemical assays that quantify the phosphorylation of a lipid substrate, such as phosphatidylinositol (4,5)-bisphosphate (PIP2), in the presence of varying concentrations of the activator. These assays are crucial for characterizing the compound's potency and mechanism of allosteric activation. The activity is confirmed using purified PI3Kα enzyme in a cell-free system.
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| Cell Assay |
In vitro cellular assays are employed to evaluate the functional activity of UCL-TRO-1938 in a cellular context. Mouse embryonic fibroblasts (MEFs), both wild-type and PI3Kα-knockout, are treated with the compound for 24 hours. Cellular metabolic activity is then measured as a readout of PI3K pathway activation. The differential response between WT and KO MEFs confirms the PI3Kα-dependent nature of the compound's effects. Western blotting is also used to measure the phosphorylation of AKT (pAKT) as a direct marker of downstream PI3K signaling activation.
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| Animal Protocol |
In vivo animal experiments are typically conducted using male C57/BL6 mice in a model of ischemia-reperfusion injury (IRI). UCL-TRO-1938 is administered at a dose of 10 mg/kg, dissolved in DMSO. Following treatment, the cardioprotective effect is assessed by evaluating cardiac tissue damage, and the activation of the PI3K/AKT pathway is confirmed by measuring pAKT(S473) levels in the heart. This model is used to study the compound's potential for treating heart-related conditions such as ischemic injury.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of UCL-TRO-1938 are characteristic of a small molecule with a molecular weight of 456.58. It is soluble in DMSO at concentrations up to 40 mg/mL, making it suitable for in vitro and in vivo administration. For in vivo use, formulations such as a homogeneous suspension in CMC-Na or a clear solution with 5% DMSO, 40% PEG300, 5% Tween 80, and 50% ddH2O have been validated. The compound's stability and precise in vivo half-life are not detailed, but its efficacy in mouse models suggests adequate systemic exposure.
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| Toxicity/Toxicokinetics |
The toxicity profile of UCL-TRO-1938 is not extensively documented. However, in vitro studies indicate that at concentrations greater than 7.5 µM, ATP levels decrease in both PI3Kα-WT and PI3Kα-KO MEFs, suggesting potential cytotoxic or off-target effects at higher doses. The compound is intended for research use only and is not for human consumption. Standard safety precautions should be observed when handling this chemical in a laboratory setting.
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| References | |
| Additional Infomation |
UCL-TRO-1938 is a first-in-class allosteric PI3Kα activator that has garnered significant attention for its therapeutic potential in cardioprotection and neuroregeneration. Its unique mechanism of action, which involves enhancing PI3Kα activity rather than inhibiting it, distinguishes it from the many PI3K inhibitors in development. Research published in Nature in 2023 highlighted its cardioprotective and neuroregenerative effects. It is a valuable research tool for exploring the therapeutic potential of PI3K activation in various disease contexts.
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| Molecular Formula |
C27H32N6O
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|---|---|
| Molecular Weight |
456.582585334778
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| Exact Mass |
456.263
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| CAS # |
2919575-27-0
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| PubChem CID |
166451134
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| Appearance |
White to off-white solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
660
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(=O)(N1C2=C(C=CC=C2NC2C=CN=C(NC3=CC=C(N4CCN(CC)CC4)C=C3)C=2)CC1)C
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| InChi Key |
RPOHONUDGBSZDK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H32N6O/c1-3-31-15-17-32(18-16-31)24-9-7-22(8-10-24)30-26-19-23(11-13-28-26)29-25-6-4-5-21-12-14-33(20(2)34)27(21)25/h4-11,13,19H,3,12,14-18H2,1-2H3,(H2,28,29,30)
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| Chemical Name |
1-[7-[[2-[4-(4-ethylpiperazin-1-yl)anilino]pyridin-4-yl]amino]-2,3-dihydroindol-1-yl]ethanone
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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 (109.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.48 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 25.0 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: 2.5 mg/mL (5.48 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. 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 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. View More
Solubility in Formulation 3: 2.5 mg/mL (5.48 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1902 mL | 10.9510 mL | 21.9020 mL | |
| 5 mM | 0.4380 mL | 2.1902 mL | 4.3804 mL | |
| 10 mM | 0.2190 mL | 1.0951 mL | 2.1902 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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