TP-3654 is a second-generation Pim kinase inhibitor (Ki values against Pim-1/3: 5/42 nM).

Pim3:42 nM (Ki), Pim2:239 nM (Ki), Pim1:5 nM (Ki)

TP-3654在PIM-1/BAD过表达系统中表现出针对PIM-1的强效细胞性活性，平均EC50为67 nM。在使用膀胱癌细胞系UM-UC-3的体外实验中，TP-3654处理降低了phospho-BAD的水平。此外，TP-3654减少了T24和UM-UC3细胞的集落生长，证实了这两种细胞系的生长依赖于PIM-1[1]。

TP-3654（200 mg/kg，i.g.）显著降低了通过体积（游标卡尺）和最终肿瘤重量测量的UM-UC-3和PC-3肿瘤生长，同时未观察到体重显著变化或明显不良毒性[1]。

1 μM TP-3654 is tested against 336 kinases at a concentration of 10 μM ATP. IC50 determinations of phosphoinositide 3-kinase (PI3K) (α, β, δ, and γ) and all kinases inhibited by >50% from the initial screen are performed using 10-dose, three-fold serial dilutions of TP-3654 starting with 10 μM at Km ATP concentrations for each kinase[1].

When tumours of mice reach 100 to 200 mm3 by calliper measurement, mice are randomized and oral dosing of TP-3654 or vehicle control began and continued every day for 5 days with 2 days off for 18 to 21 days. Tumour volumes and body weights were determined twice a week[1].