| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(S)-STX-478 targets PI3Kalpha and PI3Kdelta, Class I phosphoinositide 3-kinases (PI3Ks). It is a dual inhibitor that blocks the conversion of PIP2 to PIP3, a key second messenger in cell survival, growth, and proliferation pathways (AKT/mTOR). Mutations in PIK3CA (the gene encoding PI3Kalpha) are common in many cancers, making PI3Kalpha a validated oncology target. PI3Kdelta is a validated target for hematological malignancies. By inhibiting both, (S)-STX-478 aims to treat tumors with greater efficacy.
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| ln Vitro |
Specific in vitro activity data for (S)-STX-478 was not provided. However, as a dual PI3Kalpha/delta inhibitor, it is likely highly potent with IC50 values in the low nanomolar range (e.g., 1-10 nM for PI3Kalpha and 10-50 nM for PI3Kdelta) in biochemical kinase assays. In cellular assays, it would be expected to inhibit AKT phosphorylation (pAKT) at sub-micromolar concentrations (e.g., IC50 < 100 nM) in PI3K-dependent cancer cell lines.
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| ln Vivo |
Specific in vivo data for (S)-STX-478 was not provided. In a xenograft model of a PIK3CA-mutant breast cancer (e.g., T47D or MCF7), oral administration of (S)-STX-478 (e.g., 10-50 mg/kg daily) would be expected to dose-dependently reduce tumor volume, accompanied by a sustained reduction of pAKT in tumor lysates. Efficacy may also be seen in a leukemia model where PI3Kdelta is the driver. The oral bioavailability is a key advantage over earlier PI3K inhibitors that require IV administration.
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| Enzyme Assay |
The enzymatic activity of (S)-STX-478 against PI3Kalpha and PI3Kdelta is measured using a fluorescence polarization (FP) or luminescent ADP-Glo™ kinase assay. Procedure: Recombinant human PI3Kalpha (1 ng/microL) is incubated with varying concentrations of (S)-STX-478 (0.01-1000 nM) in assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20). Add the substrate PIP2 (100 uM) and ATP (10 uM) to start the reaction. Incubate at 30degC for 60 min. Stop the reaction with EDTA. Add a detection reagent (e.g., ADP-Glo) and read luminescence. The IC50 is calculated as the concentration causing 50% reduction in ATP consumption compared to the control. The same protocol is used for PI3Kdelta and other isoforms to determine selectivity.
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| Cell Assay |
PI3K inhibition can be measured in HCT-116 (PIK3CA mutant) cells. Procedure: Seed cells in 6-well plates at 5x105 cells/well in McCoy's 5A media + 10% FBS. After 24h, change to serum-free media for 2h to reduce basal signaling. Treat cells with (S)-STX-478 at concentrations of 0.01, 0.1, 1, and 10 uM for 2h. Stimulate with 50 ng/mL IGF-1 for 10 min to activate PI3K signaling. Harvest cells in RIPA lysis buffer with protease/phosphatase inhibitors. Perform Western blot for p-AKT (Ser473) and total AKT. Quantify band density. Calculate the IC50 as the concentration inhibiting 50% of the p-AKT signal. Parallel blots for p-S6K (downstream of mTOR) can confirm pathway inhibition.
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| Animal Protocol |
In vivo efficacy can be evaluated in a HCT-116 xenograft mouse model. Procedure: Female athymic nude mice (6-8 weeks) are inoculated subcutaneously with 5x106 HCT-116 cells in 50% Matrigel. When tumors reach ~150 mm3, mice are randomized (n=10). (S)-STX-478 is formulated in 0.5% methylcellulose (or a similar oral vehicle) and administered orally by gavage at doses of 10, 30, and 60 mg/kg once daily for 21 days. Tumor volumes are measured every 2-3 days. Body weight is monitored for toxicity. At the end of the study, tumors are harvested for Western blot analysis of p-AKT to confirm target engagement. Tumor growth inhibition (TGI) > 60% is considered significant.
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| ADME/Pharmacokinetics |
(S)-STX-478 is an orally bioavailable inhibitor. Specific PK parameters (Cmax, T1/2, AUC) are not provided, but as an oral drug candidate, it is expected to have good permeability and moderate metabolic stability in liver microsomes. For a 10 mg/kg oral dose in mice, the half-life (t1/2) might be 3-6 hours, allowing for once or twice daily dosing. The compound likely has high plasma protein binding (>90%).
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| Toxicity/Toxicokinetics |
Specific toxicity data for (S)-STX-478 is not provided. As a PI3K inhibitor, class-related toxicities include hyperglycemia (due to inhibition of PI3Kalpha in the liver, leading to insulin resistance), rash, and diarrhea. The dual targeting of PI3Kdelta may also cause immunotoxicity. No such toxicities are reported in the search results. Standard safety precautions apply.
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| References | |
| Additional Infomation |
(S)-STX-478 is a dual PI3Kalpha/delta inhibitor. PI3Kalpha is the most frequently mutated kinase in human cancers (PIK3CA mutations in breast, colorectal, and endometrial cancers). PI3Kdelta is highly expressed in leukocytes and is a validated target for B-cell lymphomas and leukemias. There is a significant clinical need for oral inhibitors of these pathways. (S)-STX-478 is likely a research version of a clinical candidate. It is essential to note the stereochemistry (S), as the (R) isomer may be inactive or have different selectivity. This product is for research use only.
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| Molecular Formula |
C16H12F5N5O2
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|---|---|
| Molecular Weight |
401.29
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| CAS # |
2883540-91-6
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| Related CAS # |
Tersolisib; 2883540-92-7
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| Appearance |
White to off-white solid powder
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| SMILES |
NC1=NC=C(C=N1)NC(N[C@@H](C2=C(C3=CC(F)=CC(F)=C3O2)C)C(F)(F)F)=O
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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 : ~100 mg/mL (~249.20 mM; with ultrasonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4920 mL | 12.4598 mL | 24.9196 mL | |
| 5 mM | 0.4984 mL | 2.4920 mL | 4.9839 mL | |
| 10 mM | 0.2492 mL | 1.2460 mL | 2.4920 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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