N-(3-Chlorophenyl)-N'-[5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-2-thiazolyl]urea methanesulfonate (1:1)

Description

SNS-314 is a pan-Aurora kinase inhibitor (IC₅₀s = 9, 31, and 3.4 nM for Aurora A, B, and C, respectively). In a panel of 219 kinases, SNS-314 also inhibits TRKB, TRKA, FLT4, FMS, DDR2, AXL, and C-RAF (IC₅₀s = 5-100 nM). SNS-314 inhibits Aurora B phosphorylation of histone H3 in HCT116 human colorectal carcinoma cells in vitro (EC₅₀ = <16 nM) and in a mouse xenograft model at a dose of 50 mg/kg. It also inhibits tumor growth in A2780 ovarian, A375 melanoma, H1299 lung, MDA-MB-231 breast, and PC3 prostate cancer mouse xenograft models when administered biweekly for six weeks at a dose of 170 mg/kg.

Uses

SNS-314 Mesylate is a potent and selective Aurora kinase inhibitor for the treatment of advanced solid tumors.

in vivo

IC 50

Aurora A: 9 nM (IC₅₀); Aurora B: 31 nM (IC₅₀); Aurora C: 6 nM (IC₅₀)

References

[1] JOHAN D. OSLOB. Discovery of a potent and selective Aurora kinase inhibitor[J]. Bioorganic & Medicinal Chemistry Letters, 2008, 18 17: Pages 4880-4884. DOI:10.1016/j.bmcl.2008.07.073
[2] JENNIFER P ARBITRARIO. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo.[J]. Cancer Chemotherapy and Pharmacology, 2010: 707-717. DOI:10.1007/s00280-009-1076-8
[3] ERICA C VANDERPORTEN. The Aurora kinase inhibitor SNS-314 shows broad therapeutic potential with chemotherapeutics and synergy with microtubule-targeted agents in a colon carcinoma model.[J]. Molecular Cancer Therapeutics, 2009: 930-939. DOI:10.1158/1535-7163.mct-08-0754
[4] FUCHEN LIU. Targeting high Aurora kinases expression as an innovative therapy for hepatocellular carcinoma.[J]. Oncotarget, 2017: 27953-27965. DOI:10.18632/oncotarget.15853