TP-3654|TP3654|Pan-PIM kinase inhibitor

Cas No.:	1361951-15-6
Synonyms:	TP3654 ,TP 3654
SMILES:	CC(C)(C1CCC(CC1)NC2=NN3C(=NC=C3C4=CC(=CC=C4)C(F)(F)F)C=C2)O
Formula:	C₂₂H₂₅N₄OF₃
M.Wt:	418.45
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

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.
Target:	Ki: 5 nm(Pim-1), 239 nM (Pim-2), 42 nM (Pim-3)[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].
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].
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 Administration:	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:	[1]. Foulks JM, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014 May;16(5):403-12.

Cat. No.	Product name	Field of application
DC11436	YLT-11	YLT-11 is a novel and specific PLK4 inhibitor with IC50 of 22 nM and Kd of 5.2 nM.
DC10031	TP-3654	TP-3654 is a small molecule pan-Pim (PIM) kinase inhibitor.
DC7514	TCS PIM-1 1	TCS PIM-1 1 is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s >20,000 nM).
DC7503	SMI 4a	SMI-4a is a potent inhibitor of Pim1 with IC50 of 17 nM, modest potent to Pim-2, does not significantly inhibit other serine/threonine- or tyrosine-kinases.
DC10514	SMI-16a	SMI-16a is a selective Pim kinase inhibitor with IC50 values of 0.15, 0.02 and 48 μM for Pim1, Pim2 and PC3 cells, respectively.
DC7160	SGI-1776	SGI-1776 is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM; 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin.
DC7236	Pimobendan	Pimobendan is a selective inhibitor of PDE3 with IC50 of 0.32 μM.
DC10047	PIM-447 dihydrochloride	PIM447 is novel pan-PIM kinase inhibitor, including Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase.
DC10171	Hispidulin	Hispidulin is a natural flavone with a broad spectrum of biological activities. Hispidulin is a Pim-1 inhibitor with an IC50 of 2.71 μM.
DC7153	CX6258	CX-6258 is a potent, orally efficacious Pim 1/2/3 kinase(IC50=5 nM/25 nM/16 nM) inhibitor with excellent biochemical potency and kinase selectivity.