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MedKoo Cat#: 202895 | Name: TGX-221
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit.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.

Chemical Structure

TGX-221
TGX-221
CAS#663619-89-4

Theoretical Analysis

MedKoo Cat#: 202895

Name: TGX-221

CAS#: 663619-89-4

Chemical Formula: C21H24N4O2

Exact Mass: 364.1899

Molecular Weight: 364.44

Elemental Analysis: C, 69.21; H, 6.64; N, 15.37; O, 8.78

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,650.00 Ready to ship
1g USD 3,850.00 Ready to ship
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Synonym
TGX221; TGX221; TGX 221.
IUPAC/Chemical Name
7-methyl-2-morpholino-9-(1-(phenylamino)ethyl)-4H-pyrido[1,2-a]pyrimidin-4-one
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
SMILES Code
O=C1C=C(N2CCOCC2)N=C3N1C=C(C)C=C3C(NC4=CC=CC=C4)C
Appearance
Off-white to pale yellow
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
TGX-221 is a LY294002  (structure shown below) analogue, able to inhibit selectively the PI3Kβ isoform in vitro.   The observed inhibition of platelet-ECC interaction and platelet activation by tirofiban contributes to explain the mechanism of "platelet anaesthesia". TGX-221 represents a promising alternative to GP IIb/IIIa blockade and should be further investigated for use during ECC in vivo. see http://www.ncbi.nlm.nih.gov/pubmed/18327411.    
Biological target:
TGX-221 is a cell membrane permeable inhibitor of the PI3K p110β catalytic subunit.
In vitro activity:
As shown in Fig. 1A and B, TGX-221 significantly inhibited the viability of U87 and U251 cells in a dose-dependent manner. The IC50 values of TGX-221 in U87 and U251 cells were ~40 and 100 µM, respectively. This study then performed the CCK-8 assay at different time-points with the IC50 values of TGX-221. Glioblastoma cell proliferation was inhibited significantly by TGX-221 in a time-dependent manner (Fig. 1C and D). Reference: Oncol Rep. 2017 Nov; 38(5): 2836–2842. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780035/
In vivo activity:
When tumourigenesis in mouse xenograft model was studied, TGX221 significantly inhibited growth of A498 cells (Fig. 6C–D). Although tumours with either mutation in SETD2 or VHL, and both WT status did not change in size following TGX221 treatment (Fig. 6D), ACHN tumours were in general slightly larger than Caki-1 or 786O tumours (Fig. 6C). Together, this study used in vitro motility assays and in vivo models to confirm that TGX221 selectively inhibited RCC cells with VHL and SETD2 mutations and conferred inhibition to tumourigenesis of RCC with mutated target genes. Reference: Sci Rep. 2015; 5: 9465. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396071/
Solvent mg/mL mM
Solubility
DMSO 32.9 90.25
DMF 30.0 82.32
Ethanol 50.0 137.20
Ethanol:PBS (pH 7.2) (1:8) 0.5 1.37
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 364.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Yang X, Yang JA, Liu BH, Liao JM, Yuan FE, Tan YQ, Chen QX. TGX-221 inhibits proliferation and induces apoptosis in human glioblastoma cells. Oncol Rep. 2017 Nov;38(5):2836-2842. doi: 10.3892/or.2017.5991. Epub 2017 Sep 22. PMID: 29048665; PMCID: PMC5780035. 2. Győri D, Csete D, Benkő S, Kulkarni S, Mandl P, Dobó-Nagy C, Vanhaesebroeck B, Stephens L, Hawkins PT, Mócsai A. The phosphoinositide 3-kinase isoform PI3Kβ regulates osteoclast-mediated bone resorption in humans and mice. Arthritis Rheumatol. 2014 Aug;66(8):2210-21. doi: 10.1002/art.38660. PMID: 24719382; PMCID: PMC4314683. 3. Feng C, Sun Y, Ding G, Wu Z, Jiang H, Wang L, Ding Q, Wen H. PI3Kβ inhibitor TGX221 selectively inhibits renal cell carcinoma cells with both VHL and SETD2 mutations and links multiple pathways. Sci Rep. 2015 Apr 8;5:9465. doi: 10.1038/srep09465. PMID: 25853938; PMCID: PMC5396071. 4. Chen R, Zhao Y, Huang Y, Yang Q, Zeng X, Jiang W, Liu J, Thrasher JB, Forrest ML, Li B. Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude mice. Prostate. 2015 May;75(6):593-602. doi: 10.1002/pros.22941. Epub 2015 Jan 25. PMID: 25620467; PMCID: PMC4376584.
In vitro protocol:
1. Yang X, Yang JA, Liu BH, Liao JM, Yuan FE, Tan YQ, Chen QX. TGX-221 inhibits proliferation and induces apoptosis in human glioblastoma cells. Oncol Rep. 2017 Nov;38(5):2836-2842. doi: 10.3892/or.2017.5991. Epub 2017 Sep 22. PMID: 29048665; PMCID: PMC5780035. 2. Győri D, Csete D, Benkő S, Kulkarni S, Mandl P, Dobó-Nagy C, Vanhaesebroeck B, Stephens L, Hawkins PT, Mócsai A. The phosphoinositide 3-kinase isoform PI3Kβ regulates osteoclast-mediated bone resorption in humans and mice. Arthritis Rheumatol. 2014 Aug;66(8):2210-21. doi: 10.1002/art.38660. PMID: 24719382; PMCID: PMC4314683.
In vivo protocol:
1. Feng C, Sun Y, Ding G, Wu Z, Jiang H, Wang L, Ding Q, Wen H. PI3Kβ inhibitor TGX221 selectively inhibits renal cell carcinoma cells with both VHL and SETD2 mutations and links multiple pathways. Sci Rep. 2015 Apr 8;5:9465. doi: 10.1038/srep09465. PMID: 25853938; PMCID: PMC5396071. 2. Chen R, Zhao Y, Huang Y, Yang Q, Zeng X, Jiang W, Liu J, Thrasher JB, Forrest ML, Li B. Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude mice. Prostate. 2015 May;75(6):593-602. doi: 10.1002/pros.22941. Epub 2015 Jan 25. PMID: 25620467; PMCID: PMC4376584.
1: Fan K, Hu Q, Yu S, Gao Y, Li Y. SP1 Mediated PIK3CB Upregulation Promotes Gastric Carcinogenesis. J Cancer. 2024 Jan 20;15(5):1355-1365. doi: 10.7150/jca.83812. PMID: 38356702; PMCID: PMC10861831. 2: Schrottmaier WC, Kral-Pointner JB, Salzmann M, Mussbacher M, Schmuckenschlager A, Pirabe A, Brunnthaler L, Kuttke M, Maier B, Heber S, Datler H, Ekici Y, Niederreiter B, Heber U, Blomgren B, Gorki AD, Söderberg-Nauclér C, Payrastre B, Gratacap MP, Knapp S, Schabbauer G, Assinger A. Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia. Cell Rep. 2022 Nov 8;41(6):111614. doi: 10.1016/j.celrep.2022.111614. PMID: 36351402. 3: Cao K, Jiang X, Wang B, Ni Z, Chen Y. SAA1 Expression as a Potential Prognostic Marker of the Tumor Microenvironment in Glioblastoma. Front Neurol. 2022 Jun 10;13:905561. doi: 10.3389/fneur.2022.905561. PMID: 35756918; PMCID: PMC9226422. 4: Mohammed EUR, Porter ZJ, Jennings IG, Al-Rawi JMA, Thompson PE, Angove MJ. Synthesis and biological evaluation of 4H-benzo[e][1,3]oxazin-4-ones analogues of TGX-221 as inhibitors of PI3Kβ. Bioorg Med Chem. 2022 Sep 1;69:116832. doi: 10.1016/j.bmc.2022.116832. Epub 2022 May 17. PMID: 35752141. 5: Piazzi M, Bavelloni A, Cenni V, Salucci S, Bartoletti Stella A, Tomassini E, Scotlandi K, Blalock WL, Faenza I. Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells. Molecules. 2022 Apr 24;27(9):2742. doi: 10.3390/molecules27092742. PMID: 35566091; PMCID: PMC9104989. 6: Tan K, Wu W, Zhu K, Lu L, Lv Z. Identification and Characterization of a Glucometabolic Prognostic Gene Signature in Neuroblastoma based on N6-methyladenosine Eraser ALKBH5. J Cancer. 2022 Mar 28;13(7):2105-2125. doi: 10.7150/jca.69408. PMID: 35517412; PMCID: PMC9066222. 7: Erkin ÖC, Cömertpay B, Göv E. Integrative Analysis for Identification of Therapeutic Targets and Prognostic Signatures in Non-Small Cell Lung Cancer. Bioinform Biol Insights. 2022 Apr 6;16:11779322221088796. doi: 10.1177/11779322221088796. PMID: 35422618; PMCID: PMC9003654. 8: Narci K, Kahraman DC, Koyas A, Ersahin T, Tuncbag N, Atalay RC. Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells. BMC Cancer. 2022 Mar 24;22(1):320. doi: 10.1186/s12885-022-09357-y. PMID: 35331184; PMCID: PMC8953069. 9: Pinto-Benito D, Paradela-Leal C, Ganchala D, de Castro-Molina P, Arevalo MA. IGF-1 regulates astrocytic phagocytosis and inflammation through the p110α isoform of PI3K in a sex-specific manner. Glia. 2022 Jun;70(6):1153-1169. doi: 10.1002/glia.24163. Epub 2022 Feb 17. PMID: 35175663; PMCID: PMC9305764. 10: Pridham KJ, Shah F, Hutchings KR, Sheng KL, Guo S, Liu M, Kanabur P, Lamouille S, Lewis G, Morales M, Jourdan J, Grek CL, Ghatnekar GG, Varghese R, Kelly DF, Gourdie RG, Sheng Z. Connexin 43 confers chemoresistance through activating PI3K. Oncogenesis. 2022 Jan 12;11(1):2. doi: 10.1038/s41389-022-00378-7. PMID: 35022385; PMCID: PMC8755794. 11: Sudasinghe TD, Banco MT, Ronning DR. Inhibitors of Mycobacterium tuberculosis EgtD target both substrate binding sites to limit hercynine production. Sci Rep. 2021 Nov 15;11(1):22240. doi: 10.1038/s41598-021-01526-6. PMID: 34782676; PMCID: PMC8593015. 12: Zillikens H, Kasprick A, Osterloh C, Gross N, Radziewitz M, Hass C, Hartmann V, Behnen-Härer M, Ernst N, Boch K, Vidarsson G, Visser R, Laskay T, Yu X, Petersen F, Ludwig RJ, Bieber K. Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita. Front Med (Lausanne). 2021 Sep 7;8:713312. doi: 10.3389/fmed.2021.713312. PMID: 34557502; PMCID: PMC8452940. 13: Cintas C, Douche T, Dantes Z, Mouton-Barbosa E, Bousquet MP, Cayron C, Therville N, Pont F, Ramos-Delgado F, Guyon C, Garmy-Susini B, Cappello P, Burlet-Schiltz O, Hirsch E, Gomez-Brouchet A, Thibault B, Reichert M, Guillermet-Guibert J. Phosphoproteomics Identifies PI3K Inhibitor-selective Adaptive Responses in Pancreatic Cancer Cell Therapy and Resistance. Mol Cancer Ther. 2021 Dec;20(12):2433-2445. doi: 10.1158/1535-7163.MCT-20-0981. Epub 2021 Sep 22. PMID: 34552006. 14: Raj N, McEachin ZT, Harousseau W, Zhou Y, Zhang F, Merritt-Garza ME, Taliaferro JM, Kalinowska M, Marro SG, Hales CM, Berry-Kravis E, Wolf-Ochoa MW, Martinez-Cerdeño V, Wernig M, Chen L, Klann E, Warren ST, Jin P, Wen Z, Bassell GJ. Cell-type-specific profiling of human cellular models of fragile X syndrome reveal PI3K-dependent defects in translation and neurogenesis. Cell Rep. 2021 Apr 13;35(2):108991. doi: 10.1016/j.celrep.2021.108991. PMID: 33852833; PMCID: PMC8133829. 15: Zeng F, Zhang Y, Han X, Zeng M, Gao Y, Weng J. Predicting Non-Alcoholic Fatty Liver Disease Progression and Immune Deregulations by Specific Gene Expression Patterns. Front Immunol. 2021 Jan 26;11:609900. doi: 10.3389/fimmu.2020.609900. PMID: 33574818; PMCID: PMC7870871. 16: Azad AK, Zhabyeyev P, Vanhaesebroeck B, Eitzen G, Oudit GY, Moore RB, Murray AG. Inactivation of endothelial cell phosphoinositide 3-kinase β inhibits tumor angiogenesis and tumor growth. Oncogene. 2020 Oct;39(41):6480-6492. doi: 10.1038/s41388-020-01444-3. Epub 2020 Sep 2. PMID: 32879446. 17: Gündüz D, Troidl C, Tanislav C, Rohrbach S, Hamm C, Aslam M. Role of PI3K/Akt and MEK/ERK Signalling in cAMP/Epac-Mediated Endothelial Barrier Stabilisation. Front Physiol. 2019 Nov 7;10:1387. doi: 10.3389/fphys.2019.01387. PMID: 31787905; PMCID: PMC6855264. 18: Benzler M, Benzler J, Stoehr S, Hempp C, Rizwan MZ, Heyward P, Tups A. "Insulin-like" effects of palmitate compromise insulin signalling in hypothalamic neurons. J Comp Physiol B. 2019 Aug;189(3-4):413-424. doi: 10.1007/s00360-019-01220-0. Epub 2019 May 23. PMID: 31123821. 19: Schepetkin IA, Kirpotina LN, Khlebnikov AI, Balasubramanian N, Quinn MT. Neutrophil Immunomodulatory Activity of Natural Organosulfur Compounds. Molecules. 2019 May 10;24(9):1809. doi: 10.3390/molecules24091809. PMID: 31083328; PMCID: PMC6539273. 20: Gupta P, Singh P, Pandey HS, Seth P, Mukhopadhyay CK. Phosphoinositide-3-kinase inhibition elevates ferritin level resulting depletion of labile iron pool and blocking of glioma cell proliferation. Biochim Biophys Acta Gen Subj. 2019 Mar;1863(3):547-564. doi: 10.1016/j.bbagen.2018.12.013. Epub 2018 Dec 23. PMID: 30586625.