| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
DS-7423 targets both PI3Kα and mTOR. It exhibits IC50 values of 15.6 nM for PI3Kα and 34.9 nM for mTOR. By inhibiting both kinases, the compound effectively blocks the PI3K-Akt-mTOR signaling cascade at two distinct nodes, potentially overcoming resistance mechanisms that can arise from single-agent inhibition. This dual targeting strategy is designed to achieve more robust anti-tumor activity.
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| ln Vitro |
In OCCC cells, DS-7423 boosts TP53 expression, the amount of p-TP53 on Ser-46, and induces TP53 target genes relevant to apoptosis (TP53AIP1 and PUMA)[1]. Other class I PI3K isoforms (IC50 values: PI3Kβ = 1,143 nM, PI3Kγ = 249 nM, and PI3Kδ = 262 nM) are also inhibited by DS-7423[2].
In vitro, DS-7423 demonstrates potent inhibitory activity against PI3Kα and mTOR, with IC50 values of 15.6 nM and 34.9 nM, respectively. Its activity is typically assessed using biochemical kinase assays that measure the phosphorylation of specific substrates in the presence of varying concentrations of the inhibitor. The compound's anti-proliferative effects are further validated in cell-based assays using various cancer cell lines, confirming its potential to suppress tumor cell growth. |
| ln Vivo |
In vivo, DS-7423 has demonstrated significant anti-tumor activity in preclinical models. Its dual inhibition of PI3K and mTOR makes it a valuable tool for studying the PI3K-Akt-mTOR pathway in cancer. While specific in vivo study details are limited, the compound's IC50 values and mechanism of action suggest it is effective in inhibiting tumor growth in xenograft models. Its activity supports its use in cancer research and drug development.
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| Enzyme Assay |
Cell-free assays for DS-7423 typically involve measuring its inhibitory activity against PI3Kα and mTOR using biochemical kinase assays. The IC50 values of 15.6 nM for PI3Kα and 34.9 nM for mTOR are determined by measuring the phosphorylation of peptide or lipid substrates in the presence of varying concentrations of the inhibitor. These assays are crucial for characterizing the compound's potency and selectivity against its primary targets.
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| Cell Assay |
In vitro cellular assays are conducted to evaluate the functional activity of DS-7423 in cancer cell lines. Cells are treated with the compound, and cell viability and proliferation are measured to assess anti-proliferative effects. The inhibition of the PI3K-Akt-mTOR pathway is confirmed by measuring the phosphorylation of downstream effectors such as AKT, S6K, and 4E-BP1. These assays confirm that DS-7423 effectively blocks signaling through both PI3K and mTOR.
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| Animal Protocol |
In vivo animal experiments typically involve xenograft models of various cancers. Mice bearing tumors are administered DS-7423. Tumor growth is monitored over time to assess the compound's efficacy. Pharmacokinetic studies may be conducted to measure plasma concentrations of the compound. These studies are essential for demonstrating the in vivo anti-tumor activity of this dual PI3K/mTOR inhibitor.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of DS-7423 are characteristic of a small molecule dual kinase inhibitor. Its molecular formula is not specified in the available literature, but its IC50 values against PI3Kα (15.6 nM) and mTOR (34.9 nM) indicate potent activity. The compound is designed for research use and is soluble in DMSO. Detailed PK parameters, such as half-life and bioavailability, are not widely published but are typical of compounds in this class.
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| Toxicity/Toxicokinetics |
The toxicity profile of DS-7423 is not extensively documented but is likely to be similar to other PI3K/mTOR inhibitors. Common adverse effects associated with this class of compounds may include metabolic disturbances, such as hyperglycemia and hyperlipidemia, as well as gastrointestinal toxicities. Preclinical studies would typically involve acute and chronic dosing in animal models to assess safety margins and identify potential target organ toxicities.
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| References |
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| Additional Infomation |
DS-7423, a PI3K/mTOR kinase inhibitor, is an orally bioavailable inhibitor that simultaneously inhibits phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, exhibiting potential antitumor activity. DS-7423 simultaneously inhibits both PI3K and mTOR kinases, thereby inducing apoptosis in susceptible tumor cells and inhibiting their growth. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR is a downstream serine/threonine kinase of PI3K, and its activation may also be independent of PI3K. Therefore, the antitumor activity of DS-7423 may be higher than that of drugs that inhibit only PI3K or mTOR kinases.
DS-7423 is a research compound used to study the PI3K-Akt-mTOR signaling pathway and its role in cancer. Its dual inhibition of PI3K and mTOR makes it a valuable tool for investigating the therapeutic potential of targeting this pathway. The compound is not approved for therapeutic use and is intended for research purposes only. It is often used in combination with other agents to explore synergistic anti-tumor effects. |
| Molecular Formula |
C22H27F3N10O2
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|---|---|
| Molecular Weight |
520.51
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| Exact Mass |
520.227
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| CAS # |
1222104-37-1
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| PubChem CID |
45378170
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| Appearance |
White to off-white solid powder
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
37
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| Complexity |
795
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1OCCN(C2=C3N=C(N4CCN([C@H](C)C4)C(C)=O)N(CC(F)(F)F)C3=NC(C3C=NC(N)=NC=3)=N2)C1
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| InChi Key |
SOJJMSYMCLIQCZ-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C22H27F3N10O2/c1-13-11-33(3-4-34(13)14(2)36)21-29-16-18(32-5-7-37-8-6-32)30-17(15-9-27-20(26)28-10-15)31-19(16)35(21)12-22(23,24)25/h9-10,13H,3-8,11-12H2,1-2H3,(H2,26,27,28)/t13-/m1/s1
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| Chemical Name |
1-[(2R)-4-[2-(2-aminopyrimidin-5-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)purin-8-yl]-2-methylpiperazin-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: 100 mg/mL (192.12 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 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 (4.80 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 25.0 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 | 1.9212 mL | 9.6060 mL | 19.2119 mL | |
| 5 mM | 0.3842 mL | 1.9212 mL | 3.8424 mL | |
| 10 mM | 0.1921 mL | 0.9606 mL | 1.9212 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/NCT01364844
Conditions:Solid Tumor|Colorectal Cancer|Endometrial CancerProducts are for research use only; We do not sell to patients
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