XRD-0394 

XRD-0394 is a potent and orally active dual ATM and DNA-PKcs inhibitor with IC₅₀s of 0.39 nM and 0.89 nM, respectively. XRD-0394 shows selectivity over other PIKK and PI3K family members. XRD-0394 significantly enhances tumor cell killing in vitro and in vivo under therapeutic ionizing radiation conditions. XRD-0394 can potentiate the effects of PARP and topoisomerase I inhibitors in vitro^[1].

XRD-0394（20 nM、100 nM、500 nM、1000 nM；预处理 30 分钟，然后用 0-10 Gy 照射 1 小时）可抑制 ATM 和 DNA-PK 激酶的磷酸化，但不抑制 MCF7 人类肿瘤细胞中结构相关的激酶^[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

在 0 或 10 Gy 局部放射治疗前 45 分钟通过口服管饲法给予 XRD-0394 (3-10 mg/kg)，并在照射后 1 小时采集肿瘤进行靶向抑制评估，XRD-0394 可抑制体内肿瘤中 DNA-PK 和 ATM 激酶的活性^[1]。
药代动力学分析表明，10 mg/kg XRD-0394（口服管饲）导致小鼠血浆浓度在 4 小时内达到 840-1,125 ng/mL (1.6-2.1 mM)，然后在 24 小时内降至不可检测的水平^[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

527.61

C₂₆H₃₀FN₅O₄S

2595308-10-2

固体

Light yellow to brown

Room temperature in continental US; may vary elsewhere.

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• [1]. Gilmer T M, et al. A novel dual ATM/DNA-PK inhibitor, XRD-0394, potently radiosensitizes and potentiates PARP and topoisomerase I inhibitors[J]. Molecular Cancer Therapeutics, 2024.  [Content Brief]