Autor: |
Kimura, Shinya, Usuki, Kensuke, Ichinohe, Tatsuo, Ikezoe, Takayuki, Kuroda, Junya, Kasahara, Senji, Okamoto, Sho, Iizuka, Hiromitsu, Ureshino, Hiroshi, Watanabe, Tatsuro, Ro, Tokihiro, Endo, Kosuke, Kagawa, Yuka, Kurahashi, Yuki, Naito, Toshiki, Yamauchi, Takahiro |
Zdroj: |
Blood; November 2023, Vol. 142 Issue: 1, Number 1 Supplement 1 p6466-6466, 1p |
Abstrakt: |
Hypomethylating agents (HMA) are commonly used to treat high-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).Decitabine (DEC), one of the HMAs, is S phase-specifically incorporated into DNA to exert its effect, and sustained plasma concentration may increase its efficacy (Saunthararajah et al. J Clin Invest. 2015). Therefore, we developed OP-2100, an orally bioavailable prodrug of DEC. It showed equal efficacy to conventional HMAs in various blood cancer mouse models and exhibited a favorable safety profile in healthy mice (Watanabe et al. Blood. 2020; Ureshino et al. Mol Cancer Ther. 2021). In addition, it exhibited a sustained-release pharmacokinetic (PK) profile when orally administered to monkeys. In a phase I study, OP-2100 monotherapy showed the expected PK profile on patients with relapsed or refractory higher-risk MDS and CMML, and we reported the preliminary result. |
Databáze: |
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