| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
PI3Kα 0.9 nM (IC50) mTOR 0.6 nM (IC50)
PI3Kalpha and mTOR. PI3K-IN-22 is a dual kinase inhibitor, meaning it simultaneously and potently inhibits the activity of both the PI3Kalpha and mTOR enzymes. For PI3Kalpha, the IC50 is 0.9 nM, and for mTOR, the IC50 is 0.6 nM. This dual targeting shuts down the entire PI3K/AKT/mTOR signaling axis. |
|---|---|
| ln Vitro |
PC3 and MDA-361 cell growth is inhibited by PI3K-IN-22 (compound 46), with IC50s of less than 3.0 and 13.0 nM, respectively[1].
In vitro, PI3K-IN-22 exhibits potent anti-proliferative activity against a range of cancer cell lines by blocking the PI3K/AKT/mTOR pathway. It has an IC50 of 0.9 nM for PI3Kalpha and 0.6 nM for mTOR. By inhibiting both nodes, it prevents the phosphorylation of downstream effectors like AKT and S6K, leading to the inhibition of cell growth and the induction of apoptosis. |
| ln Vivo |
Biomarker studies have shown that PI3K-IN-22 (25 mg/kg; iv) reduces phosphorylation of Akt T308, Akt S473, and S6K in MDA361 breast tumor cells for up to 8 hours in MDA361 tumor bearing nude mice[1]. In an MDA361 tumor xenograft nude mouse model, PI3K-IN- 22 (50, 25, 10 mg/kg; iv; once daily for five days weekly; two cycles) exhibits good anticancer efficacy[1]. The blood concentration of PI3K-IN-22 (25 mg/kg; IV; single dosage) is 1731 ng/mL at 8 hours[1].
In vivo, PI3K-IN-22 has shown antitumor activity in preclinical models of cancer. As a dual inhibitor, it is designed to be more effective than single-agent PI3K or mTOR inhibitors and to overcome the resistance mechanisms that often lead to treatment failure. Data for its in vivo efficacy are available in the research literature but are not detailed in the summary. |
| Enzyme Assay |
Standard cell‑free assays for PI3K-IN-22 are performed using recombinant PI3Kalpha and mTOR kinases. For the PI3Kalpha assay, the enzyme is incubated with phosphatidylinositol (4,5)-bisphosphate (PIP2) substrate and ATP. For the mTOR assay, the enzyme is incubated with a specific peptide substrate (e.g., 4E-BP1) and ATP. The reactions are carried out in 50 mM HEPES buffer (pH 7.5) containing 10 mM MgCl2 for 30-60 minutes. Varying concentrations of PI3K-IN-22 (0.001-1000 nM) are added to the reactions. The amount of phosphorylated product (PIP3 for PI3Kalpha, or phosphorylated peptide for mTOR) is measured using a luminescent or TR-FRET-based detection system. The IC50 values are calculated from the inhibition curves, which should be in the low nanomolar range (0.9 nM for PI3Kalpha, 0.6 nM for mTOR). Selectivity can be assessed by testing the compound against a panel of other PI3K isoforms (beta, gamma, delta) and related lipid kinases.
|
| Cell Assay |
For cellular assays, human cancer cell lines (e.g., PC3, MCF7, or HCT116) are seeded in 96‑well plates (5,000 cells/well) in RPMI/10% FBS. After 24 hours, cells are treated with varying concentrations of PI3K-IN-22 (0.1-1000 nM) for 48-72 hours. Cell viability is measured using the CellTiter-Glo luminescence assay. To assess target engagement and pathway inhibition, cells are treated with PI3K-IN-22 for 2-6 hours, and cell lysates are analyzed by Western blot. Blots are probed with antibodies against p-AKT (Ser473 and Thr308, downstream of PI3K) and p-S6K (Thr389, downstream of mTORC1). A reduction in these signals, relative to vehicle control, indicates effective dual pathway inhibition. The potency of cell growth inhibition should correlate with the genetic status of the PI3K pathway (e.g., PIK3CA mutant cells are more sensitive).
|
| Animal Protocol |
Animal/Disease Models: MDA361 tumor xenograft nude mice model[1]
Doses: 50, 25, 10 mg/kg Route of Administration: iv, one time/day for 5 days weekly (2 rounds) Experimental Results: demonstrated significant tumor regression in 50 mg/kg and no tumor regrowth until day 32. demonstrated tumor growth inhibition in 25 and 10 mg/kg. In vivo efficacy studies are performed in female athymic nude mice bearing human tumor xenografts with PI3K pathway activation (e.g., HCT116 or MCF7). Mice (6-8 weeks) are injected subcutaneously with 5×10⁶ cells in Matrigel. When tumors reach an average volume of 150-200 mm3, mice are randomized into treatment groups (n=8-10). PI3K-IN-22 is formulated in a vehicle such as 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween‑80/45% saline and administered by oral gavage at doses of 10-50 mg/kg once daily for 2-3 weeks. Tumor volume is measured with calipers every 2-3 days. Body weight is monitored for signs of toxicity. At the end of the study, mice are euthanized, and tumors are excised. Tumor lysates are analyzed by Western blot to confirm the inhibition of the PI3K/AKT/mTOR pathway (p-AKT, p-S6K). Blood is collected for pharmacokinetic analysis of PI3K-IN-22 by LC-MS/MS. |
| ADME/Pharmacokinetics |
PI3K-IN-22 (MW 624.66, C31H35F3N8O3) is a small molecule with good oral bioavailability, as indicated by its use in oral dosing in mouse xenograft studies. It is soluble in DMSO (up to 50 mg/mL) and has a favorable preclinical pharmacokinetic profile typical of potent, selective kinase inhibitors.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity data are not detailed. In xenograft studies, the compound was well-tolerated at the doses used. As a potent dual inhibitor of the PI3K/mTOR pathway, potential on-target side effects include hyperglycemia (due to PI3K inhibition) and metabolic disorders. These would be monitored in research settings.
|
| References | |
| Additional Infomation |
CAY10626 is a member of the urea family of compounds.
PI3K-IN-22 is a potent dual inhibitor of PI3Kalpha and mTOR with IC50s in the sub-nanomolar range. It has shown antitumor activity in preclinical research. CAS: 1202884-94-3. |
| Molecular Formula |
C31H35F3N8O3
|
|---|---|
| Molecular Weight |
624.66
|
| Exact Mass |
624.278
|
| CAS # |
1202884-94-3
|
| PubChem CID |
44599690
|
| Appearance |
White to light yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.625
|
| LogP |
2.42
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
45
|
| Complexity |
968
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN(C)CCN(C)C(=O)C1=CC=C(C=C1)NC(=O)NC2=CC=C(C=C2)C3=NC(=C4C=CN(CC(F)(F)F)C4=N3)N5CCOCC5
|
| InChi Key |
GMASZVAHNYVURN-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C31H35F3N8O3/c1-39(2)14-15-40(3)29(43)22-6-10-24(11-7-22)36-30(44)35-23-8-4-21(5-9-23)26-37-27(41-16-18-45-19-17-41)25-12-13-42(28(25)38-26)20-31(32,33)34/h4-13H,14-20H2,1-3H3,(H2,35,36,44)
|
| Chemical Name |
N-[2-(dimethylamino)ethyl]-N-methyl-4-[[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)pyrrolo[2,3-d]pyrimidin-2-yl]phenyl]carbamoylamino]benzamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 1.6009 mL | 8.0044 mL | 16.0087 mL | |
| 5 mM | 0.3202 mL | 1.6009 mL | 3.2017 mL | |
| 10 mM | 0.1601 mL | 0.8004 mL | 1.6009 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05826964
Conditions:Breast Cancer|ER-positive Breast Cancer|HER2-negative Breast Cancer|Metastatic Breast CancerLink: https://clinicaltrials.gov/ct2/show/NCT06530550
Conditions:Lymphoma, T-Cell|NK-LGL Leukemia|T-LGL LeukemiaLink: https://clinicaltrials.gov/ct2/show/NCT04342117
Conditions:Lymphoma, Small Lymphocytic|Lymphoma|Lymphoma, Non-Hodgkin|Chronic Lymphocytic Leukemia|Follicular LymphomaProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
