AT9283是一种有效的JAK2/3抑制剂，IC50为1.2 nM/1.1 nM；对Aurora A/B， Abl(T315I)也有效。在体外, AT9283有效抑制多种激酶，包括 Aurora A, Aurora B, JAK3, JAK2和 Abl，IC50分别为3 nM, 3 nM, 1.1 nM, 1.2 nM 和 4 nM。AT9283 作用于HCT116 细胞，通过抑制Aurora B 激酶活性，产生明显的多倍体表现型，IC50为30 nM。而且, AT9283也有效抑制HCT116形成集落。

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

Ethanol ：36 mg/mL (94.4 mM)
DMSO ：71 mg/mL (186.1 mM)

JAK3 ,JAK2 ,Aurora A ,Aurora B ,Abl1 (T315I)

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.

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 (Fp.o. = 24%).

A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies.
Arkenauet al. Ann Oncol. 2012 May;23(5):1307-13. PMID:

分子结构图