898280-07-4 Usage
Uses
Used in Oncology:
XL 228 is used as a targeted protein kinase inhibitor for treating patients with solid tumors or multiple myeloma.
Used in COVID-19 Research:
XL 228 is used as a research product for investigating its potential applications in the context of COVID-19.
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].
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.
Check Digit Verification of cas no
The CAS Registry Mumber 898280-07-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,9,8,2,8 and 0 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 898280-07:
(8*8)+(7*9)+(6*8)+(5*2)+(4*8)+(3*0)+(2*0)+(1*7)=224
224 % 10 = 4
So 898280-07-4 is a valid CAS Registry Number.
898280-07-4Relevant articles and documents
Process development and multikilogram syntheses of XL228 utilizing a regioselective isoxazole formation and a selective SNAr reaction to a pyrimidine core
Guz, Nathan R.,Leuser, Helena,Goldman, Erick
, p. 1066 - 1073 (2013/09/12)
Route scouting, process development, and multikilogram syntheses of an IGF-1R/Src/Bcr-Abl inihibitor are reported. Key aspects of the developed route are a regioselective [3 + 2] isoxazole formation on a pyrimidine core and a selective SNAr addition of an aryl amine to a symmetrical dichloro substituted pyrimidine. The route contains six synthetic steps and was demonstrated twice on scale, delivering 4.6 and 11.2 kg (25% and 16% overall yield), for Phase I clinical studies.
Methods of Using IGFIR and ABL Kinase Modulators
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, (2009/09/28)
The invention provides methods of treating cancer with a compound which inhibits kinases, more specifically IGF1R and Abl, in combination with treatments(s) selected from surgery, radiation, monoclonal antibody, bone marrow or peripheral blood stem cell t
Pyrimidine Derivatives As Kinase Modulators and Method of Use
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Page/Page column 147, (2008/12/08)
The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wildtype Abl. The invention provides compounds for modulating protein kinase enz
