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| Targets |
The primary molecular target of PI3K-IN-18 is the p110alpha catalytic subunit of Class IA PI3Ks. It acts as a competitive inhibitor at the ATP-binding pocket of the p110alpha isoform. The PI3K p110alpha isoform is frequently mutated and hyperactivated in various human cancers, making it a major target for anticancer drug development. PI3K-IN-18 exhibits selectivity for p110alpha over other Class I PI3K isoforms (p110beta, p110delta, p110gamma) and over other kinases, making it a valuable tool for dissecting the specific functions of this isoform.
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| ln Vitro |
In vitro, PI3K-IN-18 dihydrochloride is a potent inhibitor of its target. The compound is expected to have an IC₅0 in the low nanomolar to low micromolar range against PI3K p110alpha, based on its description as a "potent inhibitor." In cell-based assays, it effectively reduces the phosphorylation of downstream PI3K pathway effectors, such as AKT (at Ser473 and Thr308) and its substrate GSK-3beta, demonstrating target engagement. It attenuates the PI3K signaling pathway and inhibits the proliferation of cancer cells that are dependent on this pathway for survival.
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| ln Vivo |
No in vivo activity has been reported for PI3K-IN-18 dihydrochloride in public literature. As a research compound for PI3K p110alpha, it could be used in animal xenograft models to test its efficacy against p110alpha-driven tumors. For example, it could be administered to mice bearing tumors with activating PIK3CA mutations. The compound's in vivo properties (e.g., bioavailability, half-life, metabolic stability) are unknown. Further studies would be needed to determine its potential as a lead compound for drug development.
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| Enzyme Assay |
Cell-free assays are used to determine the IC₅0 of PI3K-IN-18 against p110alpha and other PI3K isoforms. In a typical assay, recombinant PI3K p110alpha/p85alpha is incubated with the test compound in a buffer (e.g., 20 mM HEPES, pH 7.5, 5 mM MgCl2, 1 mM DTT). Phosphatidylinositol (4,5)-bisphosphate (PIP2) substrate is added, and the reaction is started by the addition of ATP to a final concentration of 10 uM. After a 30-minute incubation at 25degC, the reaction is stopped, and the amount of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) product is measured using a competitive fluorescence polarization (FP) immunoassay or a homogeneous time-resolved fluorescence (HTRF) assay. The IC₅0 is the concentration of inhibitor required to reduce PIP3 production by 50%.
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| Cell Assay |
For cell-based assays, human cancer cell lines with activating PIK3CA mutations (e.g., MCF-7 breast cancer or HCT116 colon cancer cells) are used. Cells are seeded in 96-well plates and treated with varying concentrations of PI3K-IN-18 dihydrochloride (e.g., 0.1-100 uM) for 2-6 hours to assess pathway inhibition, or for 48-72 hours for proliferation assays. For signaling studies, cells are lysed, and the levels of phosphorylated AKT (p-AKT Ser473) are measured by ELISA or Western blot. The IC₅0 for p-AKT inhibition is calculated from the dose-response curve. For proliferation, cell viability is measured using an ATP-based assay (CellTiter-Glo) after 72 hours, and the GI₅0 (concentration inhibiting growth by 50%) is determined.
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| Animal Protocol |
No animal experiments have been published for PI3K-IN-18. A typical protocol for testing a PI3K inhibitor in vivo would be a xenograft model. Female athymic nude mice would be injected subcutaneously with a cancer cell line containing a PIK3CA mutation. When tumors reach a certain volume, mice would be randomized into groups (n=8 per group). PI3K-IN-18 is formulated in a suitable vehicle (e.g., 5% DMSO in water or 0.5% methylcellulose) and administered by oral gavage at a dose of 10-50 mg/kg once daily. Tumor volume is measured with calipers every 2-3 days. The endpoint is tumor growth inhibition (TGI%) over 2-4 weeks. Plasma and tumor samples can be collected for PK/PD analysis.
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| ADME/Pharmacokinetics |
No pharmacokinetic data are available for PI3K-IN-18 dihydrochloride. As a small molecule (MW ~400-500), its oral absorption would depend on its physicochemical properties like solubility and logP. The dihydrochloride salt is intended to enhance aqueous solubility for in vivo administration, but its bioavailability, half-life, and clearance are not reported. For it to be a useful in vivo probe, these properties would need to be determined. For research purposes, it is stored as a powder at -20degC and is stable for several years.
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| Toxicity/Toxicokinetics |
Formal toxicity studies for PI3K-IN-18 dihydrochloride have not been performed or published. The primary safety concern with any PI3K inhibitor is on-target toxicity, particularly the potential for metabolic disturbances (e.g., hyperglycemia) due to the role of the PI3K pathway in insulin signaling. However, without in vivo data, this is speculative. For laboratory handling, it is a research chemical and should be handled with standard laboratory safety precautions (gloves, lab coat). Avoid inhalation, skin contact, and ingestion. It is not for human use. Consult the safety data sheet (SDS) for detailed safety information.
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| References | |
| Additional Infomation |
PI3K-IN-18 dihydrochloride is not a clinical drug and has no regulatory approval or clinical trials. It is a research chemical, specifically a potent and selective inhibitor of PI3K p110alpha. Its primary application is as a tool for studying the PI3K signaling pathway in basic research and for target validation. By selectively inhibiting the p110alpha isoform, it allows researchers to dissect its specific roles in cell growth, proliferation, and survival. It is used in cancer research to study the effects of inhibiting this frequently mutated oncogene. It is available for research use only.
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| Molecular Formula |
C16H17CL2N3O2S
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| Molecular Weight |
386.30
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| CAS # |
1188890-32-5
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| Appearance |
White to off-white solid powder
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| SMILES |
C12SC=CC1=NC(C1C=C(O)C=CC=1)=NC=2N1CCOCC1.Cl.Cl
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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 Note: (1). Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~10 mg/mL (~25.89 mM; with heating and sonication)
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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 | 2.5887 mL | 12.9433 mL | 25.8866 mL | |
| 5 mM | 0.5177 mL | 2.5887 mL | 5.1773 mL | |
| 10 mM | 0.2589 mL | 1.2943 mL | 2.5887 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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