| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
| Targets |
PI3Kδ 1 nM (IC50) PI3Kα 51 nM (IC50) PI3Kβ 29 nM (IC50) PI3Kγ 37 nM (IC50)
|
|---|---|
| ln Vitro |
FD223 demonstrates significant anti-proliferative effects on the p110δ-positive AML cell lines KG-1, MOLM-16, HL-60, and EOL-1, with IC50 values of 2.82 μM, 5.82 μM, 0.87 μM, and 2.25 μM, in that order. With an IC50 value of 23.13 μM, FD223 exhibits weak anti-proliferative activity against the p110δ unexpressed MM.1R cell line[1]. The phosphorylation of Akt (Ser473) is dose-dependently reduced by FD223 (MOLM-16 cells; 0.1-5 μM; 16 hours), which is consistent with the positive control Idelalisib and shows that the PI3K/Akt pathway is blocked in MOLM-16 cells[1]. Like its positive control Idelalisib, FD223 (MOLM-16 cells; 24 hours; 1–5 μM) also stops the cell cycle at the G1 phase[1]. Cellular apoptosis is dose-dependently induced by FD223 (1–5 μM; 48 hours)[1].
|
| ln Vivo |
In the MOLM-16 xenograft model, FD223 (20 and 40 mg/kg; po, per day for 14 consecutive days) exhibits strong anticancer effectiveness with a 49% tumor volume decrease at a dose of 40 mg/kg/day (po). The preliminary safety assessment of the drug indicates no appreciable toxicity[1]. Following intravenous administration, FD223 (iv; dose of 2 mg/kg; po; 10 mg/kg rats) has a moderate plasma clearance rate (C = 0.191 L·h–1·kg–1). It has good oral plasma exposures (AUC0-∞>9000 h·ng/mL), an adequate oral bioavailability (17.6%), a half-life (t1/2) of 3.74 h, and a Cmax of 1104 ng/mL in the po route[1].
|
| Cell Assay |
Apoptosis Analysis[1]
Cell Types: MOLM-16 cells Tested Concentrations: 1-5 μM Incubation Duration: 48 hrs (hours) Experimental Results: Dose-dependently induced cellular apoptosis, which is superior to that of positive control Idelalisib. Western Blot Analysis[1] Cell Types: MOLM-16 cells Tested Concentrations: 0.1-5 μM Incubation Duration: 16 hrs (hours) Experimental Results: Dose-dependently decreased phosphorylation of Akt (Ser473). |
| Animal Protocol |
Animal/Disease Models: MOLM-16 xenograft model of BALB/c nude mice[1]
Doses: 20 and 40 mg/kg Route of Administration: Po, per day for 14 days Experimental Results: demonstrated a dose-dependent tumor growth inhibition (TGI) of 31% for 20 mg/kg and 49% for 40 mg/kg |
| References |
[1]. Yang C, et al. Bioisosteric replacements of the indole moiety for the development of a potent and selective PI3Kδ inhibitor: Design, synthesis and biological evaluation [published online ahead of print, 2021 Jun 21]. Eur J Med Chem. 2021;223:113661.
|
| Molecular Formula |
C17H12CLN5O2S
|
|---|---|
| Molecular Weight |
385.83
|
| CAS # |
2050524-24-6
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| SMILES |
C1(S(NC2=CC(C3=CN=C4NN=CC4=C3)=CN=C2Cl)(=O)=O)=CC=CC=C1
|
| 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) |
DMSO : 100 mg/mL (259.18 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.48 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 (6.48 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5918 mL | 12.9591 mL | 25.9182 mL | |
| 5 mM | 0.5184 mL | 2.5918 mL | 5.1836 mL | |
| 10 mM | 0.2592 mL | 1.2959 mL | 2.5918 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
