Table 1.

Antitumor efficacy of ENMD-2076 in xenograft models

ModelInitial tumor volume, mm3 (d)Dose, mg/kg% TGI (day of treatment)Regressions% Regression (day of treatment)Comments
HCT-116 colon carcinoma200 (10)100a b.i.d.89 (20)0/9
200a b.i.d.7/754 (20)2/9 deaths
HT29 colon carcinoma400 (18)50 q.d.57 (27)0/8
100 q.d.62 (27)4/8
200 q.d.90 (27)7/8
CT-26 syngeneic mouse colon carcinoma120 (9)50 q.d.−8 (26), NS0/10
100 q.d.21 (26), NS0/8
200 q.d.24 (26), NS0/7
A375 melanoma100 (21)35 q.d.13 (18), NS0/10
76 q.d.42 (18), NS0/10
151 q.d.81 (18)0/10
302 q.d.98 (18)3/91/10 death; drug was held from d 13–16
MDA-MB-231 mammary orthotopic150 (21)50a q.d.62 (27)0/8
100a q.d.94 (27)1/8
200a q.d.99 (27)4/8
300 (32)75 q.d.54 (18)0/10
302 q.d.99 (18)4/10
450 (33)200 q.d.96 (17)1/9
1740 (50)200 q.d.7/954 (14)
H929 multiple myeloma300 (18)75 q.d.69 (20)0/5
150 q.d.88 (20)0/4
225 q.d.88 (20)0/5
OPM-2 multiple myeloma200 (20)75 q.d.56 (10)0/6
150 q.d.59 (10)1/6
225 q.d.86 (10)1/6
900 (30)225 q.d.4/465 (11)
MV4;11 acute myelogenous leukemia450 (34)50a q.d.4/6 (3/6 PR, 1/6 CR)32 (25)
100a q.d.6/6 (4/6 PR, 2/6 CR)96 (25)
150a q.d.6/6 (4/6 PR, 2/6 CR)99 (25)
25a b.i.d.99 (25)3/6 (3 PR)
50a b.i.d.5/6 (4/6 PR, 1/6 CR)83 (25)
HL60 acute promyelocytic leukemia700 (36)75a q.d.77 (27)2/8
150a q.d.83 (27)3/7

NOTE: Treatment was initiated after the stated number of days when the specified tumor volume was reached. Animals were dosed with ENMD-2076 in water unless otherwise indicated.

Abbreviations: TGI, tumor growth inhibition; b.i.d., twice a day dosing; q.d., once a day dosing; NS, not significant; PR, partial regression; and CR, complete regression.

  • aIn these studies, the compound used was the free base of ENMD-2076 formulated in 0.075% carboxymethylcellulose, 0.085% Tween 80 in water. Data on file indicate that the 2 compounds have equivalent biological activity on a molar basis. To calculate an equivalent dose of ENMD-2076, multiply by 1.51.