1088965-37-0 Usage
Uses
GSK 923295 is the first potent, CENP-E-selective inhibitor that has been tested in Phase I clinical trials for treatment of Refractory Cancers.
Biological Activity
gsk923295 is a specific inhibitor of cenp-e kinesin motor with ic50 value of 3.2 nm [1].centromere-associated protein e (cenp-e) is a mitotic kinesin, which is the connect of mitosis process with the mitotic checkpoint signaling. it interacts with spindle microtubules and contribute to the chromosome alignment, and thus it regulates the cell-cycle transition from metaphase to anaphase.when asynchronous cultured cells were exposed to gsk923295, the penetrant cell-cycle delay in mitosis was observed, which accompanied with morphological changes similar to rnai-mediated knockdown of cenp-e mrna. it indicated a significant inhibition of cenp-e by gsk923295. in the presence of gsk9232195, cenp-e microtubule (mt)-stimulated atpase showed a dramatic slowing of release of adp and pi, where the atp-bound form was stabilized and the activity of cenp-e was inhibited. this observation suggested gsk923295 inhibited cenp-e via the suppression of mt-stimulated atpase [1].in mouse model, mice bearing xenografts of the colo205 colon tumor cell line were administered with gsk923295 of 125 mg/kg. the result showed gsk923295-induced cell-cycle changes of tumor cells and increased scattered apoptosis body. additionally, long-term study via measuring tumor volume revealed significant antitumor activity of gsk923295, in a manner of dose-dependent [1].
references
[1] wood k w et al. , antitumor activity of an allosteric inhibitor of centromere-associated protein-e. 2010, 107 (13): 5839-5844.
Check Digit Verification of cas no
The CAS Registry Mumber 1088965-37-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,8,8,9,6 and 5 respectively; the second part has 2 digits, 3 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1088965-37:
(9*1)+(8*0)+(7*8)+(6*8)+(5*9)+(4*6)+(3*5)+(2*3)+(1*7)=210
210 % 10 = 0
So 1088965-37-0 is a valid CAS Registry Number.
1088965-37-0Relevant articles and documents
Discovery and development of an efficient, scalable, and robust route to the novel CENP-E inhibitor GSK923295A
Bellingham, Richard,Buswell, A. Mark,Choudary, Bernie M.,Gordon, Andrew H.,Moore, Steve O.,Peterson, Matthew,Sasse, Mike,Shamji, Amin,Urquhart, Michael W. J.
, p. 1254 - 1263 (2011/04/24)
The discovery and development of an efficient manufacturing route to the CENP-E inhibitor 3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)- 1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl} -4-[(1-methylethyl)oxy]benzamide (GSK923295A) is described. The existing route to GSK923295A was expensive, nonrobust, used nonideal reagents, and consistently struggled to deliver the API needed for clinical studies. The new synthesis commences from the readily available l-phenylalaninol, which is smoothly converted through to GSK923295A using key Friedel-Crafts acylation as well as selective acylation chemistries. Downstream chemistry to GSK923295A is both high yielding and robust, and the resulting process has been demonstrated first on the kilo scale and subsequently in the pilot plant where 55 kg was successfully prepared. The resulting process is simple, uses cheaper raw materials, is greener in that it avoids using aluminum, tin, and bromination chemistries, and obviates the need for chromatographic purification. Also discussed are the route derived impurities, how they were unambiguously prepared to confirm structure and processing amendments to control their formation, and enhancements to the new process to facilitate future processing.
