TGX-221

Catalog No.S1169 Batch:S116901

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Technical Data

Formula

C21H24N4O2
Molecular Weight 364.44 CAS No. 663619-89-4
Solubility (25°C)* In vitro DMSO 12 mg/mL (32.92 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description TGX-221 is a p110β-specific inhibitor with IC50 of 5 nM in a cell-free assay, 1000-fold more selective for p110β than p110α.
Targets
p110β [5]
(Cell-free assay)		 p110δ [5]
(Cell-free assay)
5 nM 0.1 μM
In vitro 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. [1] TGX-221 inhibits platelet-ECC interaction, platelet aggregation and platelet-granulocyte binding in an extracorporeal circulation (ECC) model. [2] 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. [3]
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. [4]

Protocol (from reference)

Kinase Assay:[1]
  • Lipid kinase activity

    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:[3]
  • Cell lines

    PC3 cells

  • Concentrations

    ~20 μM

  • Incubation Time

    24-72 hours

  • Method

    For measurement of proliferation, 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.
Animal Study:[3]
  • Animal Models

    FeCl3-induced arterial thrombosis in mice

  • Dosages

    0.3 + 0.3, 1 + 1, 3 + 3 mg/kg + mg/kg/hour

  • Administration

    Administered via i.v.

Customer Product Validation

Data from [Mol Med, 2012, 18, 336-45]

Data from [Mol Med, 2012, 18, 336-45]

Data from [Mol Med, 2012, 18, 336-45]

, , Saraswati Sukumar of Johns Hopkins University School of Medicine

Selleck's TGX-221 has been cited by 96 publications

Machine learning-based identification of lower grade glioma stemness subtypes discriminates patient prognosis and drug response [ Comput Struct Biotechnol J, 2023, 21:3827-3840] PubMed: 37560125
Pan-PI3K inhibition with copanlisib overcomes Treg- and M2-TAM-mediated immune suppression and promotes anti-tumor immune responses [ Clin Exp Med, 2023, 10.1007/s10238-023-01227-6] PubMed: 37935952
Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatment [ Nat Commun, 2022, 13(1):182] PubMed: 35013322
Long noncoding RNA-mediated activation of PROTOR1/PRR5-AKT signaling shunt downstream of PI3K in triple-negative breast cancer [ Proc Natl Acad Sci U S A, 2022, 119(43):e2203180119] PubMed: 36269860
Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia [ Cell Rep, 2022, 41(6):111614] PubMed: 36351402
The Lectin LecB Induces Patches with Basolateral Characteristics at the Apical Membrane to Promote Pseudomonas aeruginosa Host Cell Invasion [ mBio, 2022, 13(3):e0081922] PubMed: 35491830
Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development [ Int J Mol Sci, 2022, 23-1810600] PubMed: 36142542
The Pro-Fibrotic Response to Lens Injury Is Signaled in a PI3K Isoform-Specific Manner [ Biomolecules, 2022, 12-91181] PubMed: 36139020
Whole-genome CRISPR screening identifies PI3K/AKT as a downstream component of the oncogenic GNAQ-Focal Adhesion Kinase signaling circuitry [ J Biol Chem, 2022, S0021-9258(22)01309-6] PubMed: 36596361
Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells [ Molecules, 2022, 27(9)2742] PubMed: 35566091

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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