| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
TGX-221 is a novel, potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit with potential anticancer activity. TGX221 selectively inhibits renal cell carcinoma cells that have both VHL and SETD2 mutations and connects various pathways. In nude mice, the prostate cancer xenograft tumor is inhibited by TGX221. ccRCC with both VHL and SETD2 mutations can be inhibited specifically by TGX221. Cancer cells with PTEN and CDKN2A mutations were also the target of TGX221. Inhibiting cell motility and tumorigenesis in ccRCC cells with VHL and SETD2 mutations was another area in which TGX221 demonstrated notable selectivity. For ccRCC with VHL and SETD2 mutations, the novel inhibitor TGX221 has a high level of selectivity.
| Targets |
p110β (IC50 = 8.5 nM); p110δ (IC50 = 211 nM)
|
|---|---|
| ln Vitro |
The activity of TGX-221 against different isoforms is measured in an in vitro PI3K assay using multiple preparations of recombinant p85/p110. With an IC50 of 211 nM, TGX-221 exhibits slow potency to p110. Additionally, TGX-221 partially inhibits the phosphorylation of Ser473 of PKB that insulin causes in J774.2 macrophage cells. [1] A platelet-ECC interaction, platelet aggregation, and platelet-granulocyte binding model using extracorporeal circulation (ECC) is inhibited by TGX-221.[2] A recent study demonstrates that PC3 cells exhibit inhibition of proliferation following treatment with TGX-221 (0.2, 2, and 20 μM), along with a notable decrease in the activity of the p110β PI3K isoform. [3]
|
| ln Vivo |
In a mouse model, integrated blood flow is improved over 30 minutes by TGX-221 at doses 1 + 1 (49%) and 3 + 3 (88%) as an anti-thrombotic agent. In addition, TGX-221 doses of 3 + 3 (median 1560) and 1 + 1 (1305) cause an increase in tail bleeding time(BT) (sec), and all TGX-221 groups experience an increase in mean renal BT (sec).[4]
|
| Enzyme Assay |
IC50 values are measured using a standard lipid kinase activity with PI as a substrate. (i)100 μM cold ATP is used instead of 10 μM, (ii) 1% DMSO is used, and (iii) [γ-33P]ATP is used instead of [γ-32P]ATP. A phosphorimager screen is used to quantify the TLC plates. The reported IC50 values were calculated using non-linear regression analysis based on at least three independent experiments that were carried out repeatedly using different recombinant protein preparations.
|
| Cell Assay |
Cells are plated in triplicate in 96-well culture plates and allowed to attach for the duration of the incubation period in order to measure cell proliferation. A total of 24, 48, and 72 hours are spent incubating the cells with TGX-221. A crystal violet staining-based colorimetric assay is used to quantify cells at predetermined time intervals. In a nutshell, 100 μl of 2.5% glutaraldehyde solution is added, and 30 minutes are spent incubating the cells at room temperature. Plates are immersed in PBS solution three times to wash them. Prior to binding dye solubilization in 100 μL of 10% acetic acid, plates are air-dried and stained by adding 100 L of 0.1% solution of crystal violet dissolved in deionized water and incubating for 20 minutes at room temperature. Excess dye is removed by extensive washing with deionized water. A microplate reader operating at 570 nm is used to directly measure the optical density of dye extracts in plates.
|
| Animal Protocol |
Rats are randomly assigned to treatment groups that contain the drug wortmannin (an irreversible non-specific PI3K inhibitor), the vehicle propylene glycol (0.25 mL/kg), LY294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; a reversible non-specific PI3K inhibitor), and IC87114 (2-[(6-aminopurin- 9-yPI3K p110 antagonist 5-methyl-3-(2-methylphenyl)quinazolin-4-one (2.5 mg/kg) and the selective PI3K p110β antagonist TGX221 (2.5 mg/kg). In the tail bleeding experiments, rats are randomLy assigned to drug treatment groups consisting of LY294002 (10 mg/kg), IC87114 (2.5 mg/kg), wortmannin (5 mg/kg), TGX221 (2.5 or 25 mg/kg), heparin (100 U/kg), aspirin (2× 200 mg/kg p.o.)± heparin (100 U/kg), and aspirin (2× 200 mg/kg p.o.) combined with heparin (100 U/kg) and TGX221 (2.5 mg/kg). All medications—aside from aspirin—are given as a slow (over ≈45-60 s) intravenous bolus into the jugular vein. Two oral doses of aspirin (200 mg/kg suspended in 15% gum arabic in water) are given, the first 24 hours before the experiment and the second one hour before it begins.
|
| References | |
| Additional Infomation |
9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone is a pyridopyrimidine.
|
| Molecular Formula |
C21H24N4O2
|
|---|---|
| Molecular Weight |
364.4409
|
| Exact Mass |
364.189
|
| Elemental Analysis |
C, 69.21; H, 6.64; N, 15.37; O, 8.78
|
| CAS # |
663619-89-4
|
| Related CAS # |
663619-89-4
|
| PubChem CID |
9907093
|
| Appearance |
Off-white to pale yellow
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
557.3±60.0 °C at 760 mmHg
|
| Flash Point |
290.8±32.9 °C
|
| Vapour Pressure |
0.0±1.5 mmHg at 25°C
|
| Index of Refraction |
1.646
|
| LogP |
3.19
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
27
|
| Complexity |
710
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O1C([H])([H])C([H])([H])N(C2=C([H])C(N3C([H])=C(C([H])([H])[H])C([H])=C(C3=N2)C([H])(C([H])([H])[H])N([H])C2C([H])=C([H])C([H])=C([H])C=2[H])=O)C([H])([H])C1([H])[H]
|
| InChi Key |
CPRAGQJXBLMUEL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H24N4O2/c1-15-12-18(16(2)22-17-6-4-3-5-7-17)21-23-19(13-20(26)25(21)14-15)24-8-10-27-11-9-24/h3-7,12-14,16,22H,8-11H2,1-2H3
|
| Chemical Name |
9-(1-anilinoethyl)-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one
|
| Synonyms |
TGX221; TGX 221; TGX221
|
| 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: ~12 mg/mL (~32.9 mM)
Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: <1 mg/mL (slightly soluble or insoluble) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.43 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 12.5 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: ≥ 1.25 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 12.5 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. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1%DMSO+30% polyethylene glycol+1%Tween 80: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7439 mL | 13.7197 mL | 27.4394 mL | |
| 5 mM | 0.5488 mL | 2.7439 mL | 5.4879 mL | |
| 10 mM | 0.2744 mL | 1.3720 mL | 2.7439 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.
Biochem J. 2007 Jun 15; 404( Pt 3): 449–458. |
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
