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| Product Name: | XL 228 | | Synonyms: | XL228; XL 228;CS-1050;XL228, >=98%;XL 228;N4-(5-Cyclopropyl-1H-pyrazol-3-yl)-N2-[[3-(1-methylethyl)-5-isoxazolyl]methyl]-6-(4-methyl-1-piperazinyl)-2,4-pyrimidinediamine;2,4-Pyrimidinediamine, N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[[3-(1-methylethyl)-5-isoxazolyl]methyl]-6-(4-methyl-1-piperazinyl)-;Inhibitor,Bcr-Abl,Aurora Kinase,Src,XL228,IGF-1R,inhibit,XL 228,XL-228;N4-(5-Cyclopropyl-1H-pyrazol-3-yl)-N2-((3-isopropylisoxazol-5-yl)methyl)-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine | | CAS: | 898280-07-4 | | MF: | C22H31N9O | | MW: | 437.54 | | EINECS: | | | Product Categories: | | | Mol File: | 898280-07-4.mol |  |
| | XL 228 Chemical Properties |
| storage temp. | Store at -20°C | | solubility | ≥21.9 mg/mL in DMSO; insoluble in H2O; ≥27.6 mg/mL in EtOH with gentle warming and ultrasonic | | form | solid | | color | White to off-white |
| | XL 228 Usage And Synthesis |
| Uses | XL228 is a multi-targeted protein kinase inhibitor in patients with solid tumors or multiple myeloma. It is a COVID19-related research product. | | Biological Activity | xl228, a tyrosine kinase inhibitor, is involved in binding to and inhibiting the activities of multiple tyrosine kinases, such as the insulin-like growth factor 1 receptor (igf1r), src tyrosine kinase, and bcr-abl tyrosine kinase. blockade of these kinases may result in the inhibition of tumor angiogenesis, cell proliferation, and metastasis [1]. xl228 is a multitargeted protein kinase inhibitor targeting igf1r, the aurora kinases, igf-1r, csrc, bcr/abl and src kinases [2]. | | in vitro | xl228(5-100 nm) reduced cell survival by 10-70% in a dose and time dependent manner and inhibited migration and invasion of two tumors with high propensity to metastasize, fadu and h460. treatment with 50 and 100 nm xl228 abolished the ability of h460, a549 and fadu cells to form colony. at 10 nm, xl228 significantly increased the radiosensitivity of h460, a549 and fadu cells by enhancement factors (ef, at the survival fraction of 0.5) of 1.52, 1.31 and 1.67 respectively. but, in hn-5 cells, sensitization occurred only at 100 nm (ef = 2.27). in hn-5 cells, xl228 (100 nm)incubation induced accumulation of cells at the radiation sensitive g2/m phase of the cell cycle and induced apoptosis in 32% of cells [2]. | | in vivo | Single-dose pharmacodynamics studies demonstrate a potent effect of XL228 on BCR-ABL signaling in K562 xenograft tumors. Phosphorylation of BCR-ABL is decreased by 50% at XL228 plasma concentrations of 3.5 μM; a similar decrease in phospho-STAT5 occurred at 0.8 μM plasma concentration[3]. | | IC 50 | Aurora A: 3.1 nM (IC50); IGF-1R: 1.6 nM (IC50) | | references | [1] smith d c, britten c, garon e b. a phase i study of xl228, a multitargeted protein kinase inhibitor, in patients with solid tumors or multiple myeloma[j]. j clinoncol, 2010, 28(15s suppl: abstr 3105).
[2] matsumoto f, molkentine d, clary d o, et al. a multi-kinase inhibitor, xl228, enhanced human cancer cell radiosensitivity and suppressed cell invasion and migration[j]. cancer research, 2011, 71(8 supplement): 2487-2487.
[3] smith d c, britten c, clary d o, et al. a phase i study of xl228, a potent igf1r/aurora/src inhibitor, in patients with solid tumors or hematologic malignancies[j]. j clinoncol, 2009, 27(15 suppl): 149s. |
| | XL 228 Preparation Products And Raw materials |
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