| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
PI3Kα (IC50 = 2 nM); PI3Kβ (IC50 = 9.4 nM); PI3Kδ (IC50 = 14 nM); PI3Kγ (IC50 = 2.7 nM); mTOR (IC50 = 5.4 nM)
The primary targets of NSC-781406 are the phosphoinositide 3-kinases (PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ) and the mammalian target of rapamycin (mTOR). The compound acts as a dual inhibitor, blocking both the PI3K and mTOR signaling pathways, which are critical for cell growth, proliferation, and survival. The IC50 values for these targets are: PI3Kα (2.0 nM), PI3Kβ (9.4 nM), PI3Kγ (2.7 nM), PI3Kδ (14 nM), and mTOR (5.4 nM). |
|---|---|
| ln Vitro |
NSC781406 exhibits strong PI3K inhibition (PI3Kα IC50=2.0 nM), which results in inhibition of BEL-7404 cell proliferation (IC50=20 nM). Reasonable liver microsome stability is shown by NSC781406. Leukemia, non-small cell, lung, colon, central nervous system, melanoma, ovarian, renal, prostate, and breast cancer are among the cancers that NSC781406 exhibits cytotoxic activities against. With a mean GI50 value of 65 nM and a GI50 value of less than 10 nM against four cancer cell lines, it is effective against 60 cancer cell lines[1].
NSC-781406 is a potent inhibitor of PI3K and mTOR. It inhibits cell growth in the NCI-60 panel of cancer cell lines with a mean GI50 of 65 nM. The compound has shown cytotoxic activity against leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer in 60 cancer cell lines. It also inhibits BEL-7404 cell proliferation with an IC50 of 20 nM. |
| ln Vivo |
Treatment with 30 mg/kg of NSC781406 in the xenograft models causes statistically significant antitumor activity, with a mean decrease in relative tumor volume ratio of 52%. At 50 mg/kg, sorafenib shows a 44% inhibition ratio. With no observed mortality or appreciable weight loss, NSC781406 is well tolerated at 30 mg/kg[1].
In a BEL-7404 hepatic cancer mouse xenograft model, treatment with 30 mg/kg of NSC-781406 resulted in statistically significant antitumor activity, with a mean reduction in relative tumor volume ratio of 52%. Sorafenib, a reference compound, displayed an inhibition ratio of 44% at 50 mg/kg. NSC-781406 was well tolerated at 30 mg/kg, with no observed mortality or significant reduction in body weight. The compound exhibits reasonable liver microsomal stability. |
| Enzyme Assay |
The IC50 values for PI3K inhibition are calculated. We use PI-103 as our reference substance. The substances (NSC781406) are examined in duplicate for 10 concentrations, with the highest concentration being either 100 nM or 500 nM. Kinase buffer is used to dilute all the chemicals. In kinase buffer, three-fold, ten-point serial compound (NSC781406) dilutions are carried out[1].
A kinase inhibition assay is used to determine the IC50 values of NSC-781406 against PI3K isoforms and mTOR. The assay involves incubating the compound with the recombinant kinase, ATP, and a substrate (e.g., PIP2 for PI3K or a peptide for mTOR). The reaction is carried out in a buffer optimized for each kinase. After incubation, the amount of phosphorylated product is quantified using a homogeneous time-resolved fluorescence (HTRF) or luminescence-based assay. IC50 values are calculated from dose-response curves generated with varying concentrations of the compound. |
| Cell Assay |
Human lung adenocarcinoma cells A549), human colon cancer cells HCT-116), human breast cancer cells MDA-MB-231), and human hepatocellular carcinoma cells BEL-7404 are used to test the cytotoxic effects. These four tumor cells are diluted to a logarithmic phase density of 40,000–50,000 cells/mL. NSC781406 compounds are given to the cells for 72 hours, and then MTT solution (5 mg/mL, 20 μL) is added for an additional 4 hours at 37°C. An analysis using nonlinear regression is used to calculate IC50 values[1].
The antiproliferative activity of NSC-781406 is assessed using the NCI-60 cancer cell line panel. Cells are cultured in appropriate media and treated with varying concentrations of the compound for 48-72 hours. Cell viability is measured using a sulforhodamine B (SRB) assay. The GI50 (concentration causing 50% growth inhibition) is calculated for each cell line. The mean GI50 across the panel is reported. Specific cytotoxicity against BEL-7404 cells is also measured using a standard cell viability assay. |
| Animal Protocol |
Mice: NSC781406 is given orally once daily at a dose of 30 mg/kg for 14 days straight, alone or in combination with 50 mg/kg sorafenib. Monitoring is done of the tumor volume in relation to the vehicle-treated control mice[1].
The in vivo efficacy of NSC-781406 is evaluated in a BEL-7404 hepatic cancer mouse xenograft model. BEL-7404 human hepatocellular carcinoma cells are implanted subcutaneously into immunodeficient mice. When tumors reach a certain volume, mice are randomized into treatment groups and administered NSC-781406 at a dose of 30 mg/kg, typically via oral or intraperitoneal administration. Tumor volume and body weight are measured twice weekly. At the end of the study, tumor volumes are compared between treatment and control groups. The antitumor activity is expressed as the percentage reduction in relative tumor volume (T/C) or tumor growth inhibition (TGI) ratio. |
| ADME/Pharmacokinetics |
NSC-781406 demonstrates reasonable liver microsomal stability. Specific pharmacokinetic parameters (e.g., half-life, clearance, volume of distribution) are not detailed in the available sources. The compound is a small molecule with a molecular weight of 627.68 and is soluble in DMSO at 20 mg/mL. Standard PK studies would typically be performed to characterize its absorption, distribution, metabolism, and excretion.
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| Toxicity/Toxicokinetics |
In a BEL-7404 xenograft model, NSC-781406 was well tolerated at 30 mg/kg, with no observed mortality or significant reduction in body weight. This suggests a favorable safety profile at the efficacious dose. However, specific toxicity data (e.g., LD50, organ toxicity) are not detailed in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications.
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| References | |
| Additional Infomation |
NSC-781406 is also known as NSC781406 or NSC 781406. Its chemical name is 2,4-difluoro-N-[2-methoxy-5-[4-[3-(4-methylsulfonylpiperazin-1-yl)prop-1-ynyl]quinolin-6-yl]pyridin-3-yl]benzenesulfonamide. It has a CAS number of 1676893-24-5 and a molecular formula of C29H27F2N5O5S2. The compound is stored at -20°C for long-term stability.
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| Molecular Formula |
C29H27F2N5O5S2
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|---|---|
| Molecular Weight |
627.681990861893
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| Exact Mass |
627.142
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| Elemental Analysis |
C, 55.49; H, 4.34; F, 6.05; N, 11.16; O, 12.74; S, 10.22
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| CAS # |
1676893-24-5
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| Related CAS # |
1676893-24-5
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| PubChem CID |
127025628
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
43
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| Complexity |
1230
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C(C=N1)C2=CC3=C(C=CN=C3C=C2)C#CCN4CCN(CC4)S(=O)(=O)C)NS(=O)(=O)C5=C(C=C(C=C5)F)F
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| InChi Key |
BBRINJUWZRLWKK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H27F2N5O5S2/c1-41-29-27(34-43(39,40)28-8-6-23(30)18-25(28)31)17-22(19-33-29)21-5-7-26-24(16-21)20(9-10-32-26)4-3-11-35-12-14-36(15-13-35)42(2,37)38/h5-10,16-19,34H,11-15H2,1-2H3
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| Chemical Name |
2,4-difluoro-N-[2-methoxy-5-[4-[3-(4-methylsulfonylpiperazin-1-yl)prop-1-ynyl]quinolin-6-yl]pyridin-3-yl]benzenesulfonamide
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| Synonyms |
NSC-781406; NSC 781406; NSC781406
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| HS Tariff Code |
2934.99.03.00
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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: ~150 mg/mL (~239 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 3.75 mg/mL (5.97 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension 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 (5.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5932 mL | 7.9658 mL | 15.9317 mL | |
| 5 mM | 0.3186 mL | 1.5932 mL | 3.1863 mL | |
| 10 mM | 0.1593 mL | 0.7966 mL | 1.5932 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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