Abstract: OBJECTIVE To evaluate the toxicity of SU-142, an new analogue of apixaban, in Beagle dogs following repeated oral administration for 4 weeks. METHODS The 40 Beagle dogs were randomly divided into 4 groups included control group and SU-142 (50, 150, 300 mg·kg^-1) groups with 10 animals (5 male and 5 female) in each group. Dogs were treated orally once a day for 4 weeks with SU-142 (50, 150, 300 mg·kg^-1) or 0.5% CMC-Na as vehicle with a volume of 5 mL·kg^-1, following a recovery period of 2 weeks. During the experiment, toxicological indexes were detected, and the coagulation indexes were monitored 1, 2, 4 and 8 h after the first and last administration. RESULTS Only mild vomiting occurred in a dog in 150 mg·kg^-1 group after the first administration, and last for 7 d, without other abnormal reactions. Due to the lower incidence and mild degree, vomiting was seen to be not related with SU-142. Coagulation test showed that prothrombin time (PT) and thrombin time (TT) were significantly increased at 1 h after the first administration, and lasted through the whole treatment with markedly dose-effect and time-effect relationship. PT and TT achieved to the peak at 4 h after the last administration, while PT and TT in 300 mg·kg^-1 group reached approximately 2 times of control. Activated partial thromboplastin time (APTT) also showed a significantly increase with a dose-effect relationship. After recovered for 2 weeks, PT, TT and APTT fell to baseline. No other marked changes were observed in electrocardiogram, hematology, clinical chemistry and histopathology. CONCLUSION The main toxic target of SU-142 is coagulation (increased PT, TT and APTT), which should be an amplification of the anti-coagulation of SU-142. The toxic effect is reversible. The study don't find the effect of the miss target effect outside the mechanism of the trial product.