Benzoic acid, 4-[[[(3'R,4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-1'',2''-dihydro-2''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-[3H]indol]-5'-yl]carbonyl]amino]-, 2,2,2-trifluoroacetate (1:1)

Uses

MI-1061 TFA is a potent, orally bioavailable, and chemically stable MDM2 (MDM2-p53 interaction) inhibitor (IC50=4.4 nM; Ki=0.16 nM). MI-1061 TFA potently activates p53 and induces apoptosis in the SJSA-1 xenograft tumor tissue in mice. Anti-tumor activity[1].

Biological Activity

MI-1061 TFA is a potent, orally bioavailable, and chemically stable MDM2 (MDM2-p53 interaction) inhibitor (IC50=4.4 nM; Ki=0.16 nM). MI-1061 TFA potently activates p53 and induces apoptosis in the SJSA-1 xenograft tumor tissue in mice. Anti-tumor activity[1]. MI-1061 achieves IC50=100 and 250 nM in the SJSA-1 and HCT-116 p53+/+ cell lines, respectively, and has IC50>10000 nM in the p53 knockout cell line HCT-116 p53-/-cell line[1]. MI-1061 (100 mg/kg; p.o.; daily for 14 days) is capable of achieving tumor regression in the SJSA-1 xenograft tumor model in mice[1].

in vivo

References

[1]. Aguilar A, et al. Design of chemically stable, potent, and efficacious MDM2 inhibitors that exploit the retro-mannich ring-opening-cyclization reaction mechanism in spiro-oxindoles. J Med Chem. 2014;57(24):10486-10498.