AT9283 | CAS:896466-04-9

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Name:AT9283; 
Cat. No. :CS-0107
CAS No. :896466-04-9
Formula:C19H23N7O2
M. Wt. : 381.43
Solubility:10 mM in DMSO

AT9283 is a multi-targeted inhibitor with IC50s of 1.2 nM, 1.1 nM for JAK2 and JAK3, respectively, and is also potent to Aurora A, Aurora B and Abl(T315I).IC50 & Target: IC50: 1.2 nM (JAK2), 1.1 nM (JAK3), 3 nM (Aurora A), 3 nM (Aurora B)[1]In Vitro: AT9283 leads to a clear polyploid phenotype by inhibiting the activity of Aurora B kinase in HCT116 cells with IC50 of 30 nM. Furthermore, AT9283 also produces the potent inhibition on HCT116 colony formation[1]. AT9283 induces apoptosis in a dose and time dependent manner and inhibits cell proliferation with an IC50 [2]. AT9283 inhibits growth, induces dose dependent cytotoxicity, and inhibits STAT3 signaling pathway in MM cell lines. T9283 inhibits phospho Histone H3 and phospho Aurora A at Thr 288. AT9283 increases G2/M phase and induces apoptosis of MM cells in a time-dependent manner[3].In Vivo: In HCT116 human colon carcinoma xenograft bearing mice, AT9283 treatment (15 mg/kg and 20 mg/kg) for 16 days results in a significant tumor growth inhibition of 67% and 76%, respectively. In addition, AT9283 also exhibits a significantly longer half-life in tumors (2.5 hours) compared with plasma (0.5 hour) and modest oral bioavailability in mice[1]. AT9283 (15 mg/kg) and docetaxel (10 mg/kg) alone has modest anti-tumor activity. T9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrate a statistically significant tumor growth inhibition and enhance survival inmouse xenograft model of mantle cell lymphoma[2]. AT9283 (45 mg/kg, i.p.) inhibits tumor growth in mice. Two cycles of AT9283 45 mg/kg 14 hours after drug administration confirm decreased expression of phospho-Histone H3 and Aurora B in treated animals[3].

Santo L, et al. Antimyeloma activity of a multitargeted kinase inhibitor, AT9283, via potent Aurora kinase and STAT3 inhibition either alone or in combination with lenalidomide. Clin Cancer Res. 2011 May 15;17(10):3259-71. Qi W, et al. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas. Int J Cancer. 2012 Jun 15;130(12):2997-3005. Howard S, et al. Fragment-Based Discovery of the Pyrazol-4-yl Urea (AT9283), a Multitargeted Kinase Inhibitor with Potent Aurora Kinase Activity. Journal of Medicinal Chemistry (2009), 52(2), 379-388.