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Description: 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 with both VHL and SETD2 mutations and links multiple pathways. TGX221 blocks xenograft tumor growth of prostate cancer in nude mice. TGX221 is a selective inhibitor for ccRCC with both VHL and SETD2 mutations. TGX221 also targeted cancer cells with CDKN2A and PTEN mutations. TGX221 also exhibited significant selectivity in inhibiting cell motility and tumourigenesis of ccRCC cells with VHL and SETD2 mutations. TGX221 is a novel inhibitor with high selectivity for ccRCC with VHL and SETD2 mutations.
References: Sci Rep. 2015 Apr 8;5:9465.
Product Catalog 2023
Guide to Product Handling
Molecular Weight (MW)
364.44
Formula
C21H24N4O2
CAS No.
663619-89-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
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)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Chemical Name/Synonyms
9-(1-anilinoethyl)-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one; TGX221; TGX221; TGX 221
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In Vitro
Kinase 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) the DMSO concentration is 1%, and (iii) [γ-33P]ATP is used instead of [γ-32P]ATP. The TLC plates are quantified using a phosphorimager screen. The reported IC50 values are determined by non-linear regression analysis on the basis of at least three independent experiments repeated across multiple preparations of recombinant protein.
Cell Assay: For measurement of proliferation, PC3 cells are seeded in triplicate in 96-well culture plates and incubated overnight to allow cell attachment. The cells are incubated with TGX-221 for 24, 48, and 72 hours. At designated time intervals, cells are quantified by a crystal violet staining-based colorimetric assay. Briefly, cells are fixed by addition of 100 μl of 2.5% glutaraldehyde solution and incubated at room temperature for 30 minutes. Plates are washed three times by submersion in PBS solution. Plates are air-dried and stained by addition of 100 μL of 0.1% solution of crystal violet dissolved in deionized water and incubated for 20 minutes at room temperature, excess dye is removed by extensive washing with deionized water, and plates are air-dried prior to bound dye solubilization in 100 μL of 10% acetic acid. The optical density of dye extracts is measured directly in plates using a microplate reader at 570 nm. Drug concentration: 20 μM
The activity of TGX-221 against different isoforms is measured in an in vitro PI3K assay using multiple preparations of recombinant p85/p110. TGX-221 show slow potent to p110δ with IC50 of 211 nM. Furthermore, TGX-221 partially attenuates insulin-induced phosphorylation of Ser473 of PKB in J774.2 macrophage cells. TGX-221 inhibits platelet-ECC interaction, platelet aggregation and platelet-granulocyte binding in an extracorporeal circulation (ECC) model. A recent study shows that after treatment with TGX-221 (0.2, 2, and 20 μM), PC3 cells show inhibition of proliferation with a significant reduction of the activity of the p110β PI3K isoform.
In Vivo
As an anti-thrombotic agent, TGX-221 at doses 1 + 1 (49 %) and 3+3 (88 %) improves integrated blood flow over 30 minutes in a mouse model. In addition, Tail bleeding time (BT) (sec) increases with TGX-221 doses of 3 + 3 (median 1560) and 1 + 1 (1305) and mean renal BT (sec) also increases in all TGX-221 groups.
Animal model
FeCl3-induced arterial thrombosis in mice
Formulation & Dosage
Solubilized in 0% ethanol, 10% cremaphor, 10% N,N-dimethylacetamine, 70% distilled water; 0.1, 1, 3 mg/kg; i.v.
References
[1] Chaussade C, et al. Biochem J. 2007, 404(3), 449-458.; [2] Straub A, et al. Thromb Haemost. 2008, 99(3), 609-615.; [3] Lu XY, et al. Appl Microbiol Biotechnol. 2011, 89(5), 1423-1433.
Purity ≥98%
COA
MSDS
Biochem J. 2007 Jun 15; 404( Pt 3): 449–458.