EZM 2302

EZM 2302 is a potent and orally active CARM1 inhibitor with an IC₅₀ value of 6 nM. EZM 2302 shows antiproliferative activity and anti-tumor activity. EZM 2302 inhibits PABP1 and SMB expression^[1]. IC50 & Target:IC50: 6 nM (CARM1)^[1] In Vitro:EZM 2302 (0-20 µM; 15 days) shows antiproliferative activity activity with IC₅₀s of >20, >20, 12.2, >20, >20 µM for ZR751, MCF7, LNCAP, PC3, VCAP cells, respectively^[1].
EZM 2302 (0-5 µM; 96 h) inhibits PABP1 and SMB methylation in cells^[1]. In Vivo:EZM 2302 (37.5, 75, 150, 300 mg/kg; p.o.; twice daily for 21 days) shows anti-tumor activity in mouse^[1].
Pharmacokinetic Parameters of EZM 2302 in CD-1 mouse and Sprague-Dawley rat^[1].

Parameters	IV(CD-1 mouse)	PO(CD-1 mouse)	IV (Sprague-Dawley rat)	PO (Sprague-Dawley rat)
Dose (mg/kg)	2	10	2	10
Blood:plasma ratio	1.2	1.2	2.6	ND
Cmax(ng/mL)		177		113 ± 22.4
Tmax(h)		2.00		2.00
AUC0-last(ng.h/mL)	767	568	352 ± 30.6	453 ± 89.3
AUC0-inf(ng.h/mL)	772	577	372 ± 43.3	487 ± 102
t1/2(h)	4.22	4.55	6.21 ± 1.65	6.64 ± 1.41
Vss(L/kg)	6.53		35.6 ± 1.30
CL (mL/min/kg)	43.2		90.5 ± 10.5
Fa*Fg (%)		ND		80.7
F (%)		15.0		26.2 ± 5.45

CD-1 mouse and Sprague-Dawley rats, 2 mg/kg iv; 10 mg/kg po^[1]