CEP-37440

CEP-37440 is a potent, orally active dual FAK/ALK inhibitor with IC₅₀ values of 2.3 nM and 3.5 nM for FAK and ALK, respectively. CEP-37440 decreases the cell proliferation by blocking the autophosphorylation kinase activity of FAK1 (Tyr 397)^[1][2]. IC50 & Target:IC₅₀:2.3 nM (FAK) and 3.5 nM (ALK)^[2] In Vitro:CEP-37440 (0-3000 nM; 0-192 h) decreases the proliferation of inflammatory breast cancer (IBC) cells in a dose-dependent manner^[1].
CEP-37440 (1000 nM; 0-120 h) decreases phospho-FAK1 (Tyr 397) and maintains its low level over time in FC-IBC02, SUM 190, and KPL4^[1].
CEP-37440 (0-3000 nM; Sup-M2 and Karpas-299 cells) induces proapoptotic caspases in a dose-dependent manner^[2].
In Vivo:CEP-37440 (3-55 mg/kg; p.o.; b.i.d and q.d., for 12 d) inhibits breast tumor growth in Sup-M2 xenograftin SCID mice^[2].
CEP-37440 (30 mg/kg; p.o; once, for 24 h) inhibits tyrosine phosphorylation in Sup-M2 xenografts mice^[2].
CEP-37440 (55 mg/kg; p.o; once, for 24 h) inhibits FAK phosphorylation in CWR22 xenografts in Nude mice^[2].
CEP-37440 (1-10 mg/kg; p.o and i.v.; CD-1 mouse, Sprague-Dawley (SD) rats) has good pharmacokinetic parameters^[2].

Pharmacokinetic parameters in CD-1 mouse and Sprague-Dawley (SD) rats^[2]

	PK parameter	CD-1 mouse	SD rat
iv	dose (mg/kg)	1	1
iv	t1/2 (h)	3.0	2
iv	AUC0-∞ (ng*h/mL)	1612	4005
iv	Vd (L/kg)	2.7	0.8
iv	CL (mL/min/kg)	10	4
po	dose (mg/kg)	10	5
po	Cmax (ng/mL)	1533	1340