TP-3654
Names
[ CAS No. ]:
1361951-15-6
[ Name ]:
TP-3654
[Synonym ]:
2-[4-[[3-[3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazin-6-yl]amino]cyclohexyl]propan-2-ol
Biological Activity
[Description]:
TP-3654 is a second-generation Pim kinase inhibitor with Ki values of 5 and 42 nM for Pim-1 and Pim-3, respectively.
[Related Catalog]:
[Target]
Ki: 5 nm(Pim-1), 239 nM (Pim-2), 42 nM (Pim-3)[1]
[In Vitro]
TP-3654 demonstrates potent PIM-1 specific cellular activity in the PIM-1/BAD overexpression system with an average EC50 of 67 nM. TP-3654 treatment reduces levels of phospho-BAD in vitro using the bladder cancer cell line UM-UC-3. TP-3654 reduces colony growth of T24 and UM-UC3 cells, confirming the PIM-1–dependent growth for both cell lines[1].
[In Vivo]
Oral dosing of 200 mg/kg TP-3654 significantly reduces both UM-UC-3 and PC-3 tumor growth measured by volume (caliper) and by final tumor weight, with no significant changes in body weight or gross adverse toxicity[1].
[Cell Assay]
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].
[Animal admin]
When tumors of mice reaches 100 to 200 mm3 by caliper 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. Tumor volumes and body weights were determined twice a week[1].
[References]
[Related Small Molecules]
Chemical & Physical Properties
[ Molecular Formula ]:
C22H25F3N4O
[ Molecular Weight ]:
418.464
[ Storage condition ]:
2-8℃