WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H202895
CAS#: 663619-89-4
Description: 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.
Hodoodo Cat#: H202895
Name: TGX-221
CAS#: 663619-89-4
Chemical Formula: C21H24N4O2
Exact Mass: 364.19
Molecular Weight: 364.440
Elemental Analysis: C, 69.21; H, 6.64; N, 15.37; O, 8.78
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 | Max Conc. mg/mL | Max Conc. 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 |
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.
| 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: 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. PubMed PMID: 25853938.
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. PubMed PMID: 25620467; PubMed Central PMCID: PMC4376584.
3: Ukhanov K, Corey EA, Ache BW. Phosphoinositide 3-kinase dependent inhibition as a broad basis for opponent coding in Mammalian olfactory receptor neurons. PLoS One. 2013 Apr 9;8(4):e61553. doi: 10.1371/journal.pone.0061553. Print 2013. PubMed PMID: 23585911; PubMed Central PMCID: PMC3621990.
4: Moir LM, Trian T, Ge Q, Shepherd PR, Burgess JK, Oliver BG, Black JL. Phosphatidylinositol 3-kinase isoform-specific effects in airway mesenchymal cell function. J Pharmacol Exp Ther. 2011 May;337(2):557-66. doi: 10.1124/jpet.110.173583. Epub 2011 Feb 24. PubMed PMID: 21349933.
5: Lu XY, Ciraolo E, Stefenia R, Chen GQ, Zhang Y, Hirsch E. Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines. Appl Microbiol Biotechnol. 2011 Mar;89(5):1423-33. doi: 10.1007/s00253-011-3101-1. Epub 2011 Feb 1. PubMed PMID: 21286711.
6: Sturgeon SA, Jones C, Angus JA, Wright CE. Advantages of a selective beta-isoform phosphoinositide 3-kinase antagonist, an anti-thrombotic agent devoid of other cardiovascular actions in the rat. Eur J Pharmacol. 2008 Jun 10;587(1-3):209-15. doi: 10.1016/j.ejphar.2008.03.017. Epub 2008 Mar 29. PubMed PMID: 18455722.
(Last Updated: 4/20/2016)
