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XL228

Catalog No.
A3939
IGF1R/AURORA /FGFR1-3/ABL/SRC family kinases inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$133.00
In stock
5mg
$127.00
In stock
10mg
$170.00
In stock
25mg
$342.00
In stock
50mg
$442.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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].

Clinical trial: In a phase I study in patients with solid tumors or hematologic malignancies, XL228 showed a manageable toxicity profile and biological activity through decrease in target pathway and alternations in tumor nuclei [3].

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt437.54
Cas No.898280-07-4
FormulaC22H31N9O
SynonymsXL-228;XL 228
Solubility≥21.9 mg/mL in DMSO; insoluble in H2O; ≥27.6 mg/mL in EtOH with gentle warming and ultrasonic
Chemical Name4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine
SDFDownload SDF
Canonical SMILESCC(C)C1=NOC(=C1)CNC2=NC(=CC(=N2)NC3=NNC(=C3)C4CC4)N5CCN(CC5)C
Shipping ConditionShip with blue ice, or upon other requests.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. We do not recommend long-term storage for the solution, please use it up soon.

Quality Control

Chemical structure

XL228