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Clin Cancer Res: The efficacy and safety of ROCK-AKT dual inhibitor AT13148 for the treatment of solid tumors.

 Last Update: 2020-08-24
 Source: Internet
 Author: User

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AT13148 is an oral AGC kinase inhibitor that potentially inhibits ROCK and AKT kinases.
the previous clinical model, AT13148 showed anti-transfer and anti-proliferation activity.
the trial was designed to evaluate the efficacy and safety of AT13148 for solid tumors.
at AT13148: 3 times a week (Monday, Wednesday and Friday), 28 Mondays.
recruited a total of 51 patients.
dose of AT13148 was 5-300 mg.
, doses of 120-180-240 mg were studied in the outpatient dose increase queue.
limiting toxicity includes low blood pressure (300 mg), elevated pneumonia and liver enzymes (240 mg) and rash (180 mg).
most common side effects are fatigue, nausea, headaches and low blood pressure.
180 mg is set as the maximum tolerable dose based on tolerance.
180 mg dose, the average Cmax and APC were 400 nmol/L and 13,000 nmol/L/hour, respectively;
conclusion: AT13148 is the first double-effective ROCK-AKT inhibitor to be studied for the treatment of solid tumors.
the narrow therapeutic index and pharmacodiodynamics lead to the further development of the compound is not recommended.
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