WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205477
Description: GSK1070916, also known as NMI-900 or GSK-1070916A, is an ATP-competitive inhibitor of the serine/threonine kinases Aurora B and C with potential antineoplastic activity. Aurora B/C kinase inhibitor GSK1070916A binds to and inhibits the activity of Aurora kinases B and C, which may result in inhibition of cellular division and a decrease in the proliferation of tumor cells that overexpress the Aurora kinases B and C. Aurora kinases play essential roles in mitotic checkpoint control during mitosis, and are overexpressed by a wide variety of cancer cell types. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
MedKoo Cat#: 205477
Chemical Formula: C30H33N7O
Exact Mass: 507.27466
Molecular Weight: 507.63
Elemental Analysis: C, 70.98; H, 6.55; N, 19.31; O, 3.15
Synonym: GSK 1070916; GSK-1070916; GSK 1070916; GSK1070916A; GSK-1070916A; GSK 1070916A; NMI-900; NMI 900; NMI900.
IUPAC/Chemical Name: 3-(4-(4-(2-(3-((dimethylamino)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl)phenyl)-1,1-dimethylurea.
InChi Key: QTBWCSQGBMPECM-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H33N7O/c1-6-37-19-26(28(34-37)21-10-12-23(13-11-21)32-30(38)36(4)5)24-14-15-31-29-25(24)17-27(33-29)22-9-7-8-20(16-22)18-35(2)3/h7-17,19H,6,18H2,1-5H3,(H,31,33)(H,32,38)
SMILES Code: O=C(NC1=CC=C(C2=NN(CC)C=C2C3=C4C(NC(C5=CC=CC(CN(C)C)=C5)=C4)=NC=C3)C=C1)N(C)C
GSK1070916 is a novel ATP competitive inhibitor that is highly potent and selective for Aurora B/C kinases. Human tumor cells treated with GSK1070916 show dose-dependent inhibition of phosphorylation on serine 10 of Histone H3, a substrate specific for Aurora B kinase. Moreover, GSK1070916 inhibits the proliferation of tumor cells with EC(50) values of <10 nmol/L in over 100 cell lines spanning a broad range of tumor types. Although GSK1070916 has potent activity against proliferating cells, a dramatic shift in potency is observed in primary, nondividing, normal human vein endothelial cells, consistent with the proposed mechanism. We further determined that treated cells do not arrest in mitosis but instead fail to divide and become polyploid, ultimately leading to apoptosis. GSK1070916 shows dose-dependent inhibition of phosphorylation of an Aurora B-specific substrate in mice and consistent with its broad cellular activity, has antitumor effects in 10 human tumor xenograft models including breast, colon, lung, and two leukemia models. These results show that GSK1070916 is a potent Aurora B/C kinase inhibitor that has the potential for antitumor activity in a wide range of human cancers. [Mol Cancer Ther 2009;8(7):1808Â–17]
1: Moy C, Oleykowski CA, Plant R, Greshock J, Jing J, Bachman K, Hardwicke MA, Wooster R, Degenhardt Y. High chromosome number in hematological cancer cell lines is a negative predictor of response to the inhibition of Aurora B and C by GSK1070916. J Transl Med. 2011 Jul 15;9:110. doi: 10.1186/1479-5876-9-110. PubMed PMID: 21762492; PubMed Central PMCID: PMC3146841.
2: Zhang B, Li Y, Zhang H, Ai C. 3D-QSAR and Molecular Docking Studies on Derivatives of MK-0457, GSK1070916 and SNS-314 as Inhibitors against Aurora B Kinase. Int J Mol Sci. 2010 Nov 2;11(11):4326-47. doi: 10.3390/ijms11114326. PubMed PMID: 21151441; PubMed Central PMCID: PMC3000085.
3: Adams ND, Adams JL, Burgess JL, Chaudhari AM, Copeland RA, Donatelli CA, Drewry DH, Fisher KE, Hamajima T, Hardwicke MA, Huffman WF, Koretke-Brown KK, Lai ZV, McDonald OB, Nakamura H, Newlander KA, Oleykowski CA, Parrish CA, Patrick DR, Plant R, Sarpong MA, Sasaki K, Schmidt SJ, Silva DJ, Sutton D, Tang J, Thompson CS, Tummino PJ, Wang JC, Xiang H, Yang J, Dhanak D. Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001. doi: 10.1021/jm901870q. PubMed PMID: 20420387.
4: Medina JR, Grant SW, Axten JM, Miller WH, Donatelli CA, Hardwicke MA, Oleykowski CA, Liao Q, Plant R, Xiang H. Discovery of a new series of Aurora inhibitors through truncation of GSK1070916. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2552-5. doi: 10.1016/j.bmcl.2010.02.091. Epub 2010 Mar 1. PubMed PMID: 20335034.
5: Hardwicke MA, Oleykowski CA, Plant R, Wang J, Liao Q, Moss K, Newlander K, Adams JL, Dhanak D, Yang J, Lai Z, Sutton D, Patrick D. GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models. Mol Cancer Ther. 2009 Jul;8(7):1808-17. doi: 10.1158/1535-7163.MCT-09-0041. Epub 2009 Jun 30. PubMed PMID: 19567821.
6: Anderson K, Lai Z, McDonald OB, Stuart JD, Nartey EN, Hardwicke MA, Newlander K, Dhanak D, Adams J, Patrick D, Copeland RA, Tummino PJ, Yang J. Biochemical characterization of GSK1070916, a potent and selective inhibitor of Aurora B and Aurora C kinases with an extremely long residence time1. Biochem J. 2009 May 13;420(2):259-65. doi: 10.1042/BJ20090121. PubMed PMID: 19284385.