eCF506-d₅  (Synonyms: NXP900-d₅)

eCF506-d₅ (NXP900-d₅) is deuterated labeled eCF506 (HY-112096). eCF506 is a highly potent and orally active YES1/SRC kinase inhibitor with an IC₅₀ of 0.47 nM. eCF506 locks its target into its native “closed” conformation, thereby inhibiting both kinase activity and complex formation with protein partners. eCF506 can be used for the study of esophageal squamous cancer and breast cancer^[1][2][3].

氢、碳和其他元素的稳定重同位素已被纳入药物分子中，主要作为药物开发过程中定量的示踪剂。氘化引起了人们的关注，因为它可能影响药物的药代动力学和代谢谱^[1]。
eCF506 在 MCF7 和 MDA-MB-231 细胞中诱导非常有效的抗增殖作用。eCF506 在低纳摩尔水平抑制 SRC 和 FAK 的磷酸化，在 100 nM 时观察到完全抑制。早在研究开始 6 小时，eCF506 就以 10 nM 显著降低细胞运动性，与 dasatinib 的效果相当。eCF506 专门抑制 SFK，对 SRC 和 YES 具有亚纳摩尔 IC₅₀ 值 (IC₅₀=0.5，2.1 nM)。需要强调的是，eCF506 在 ABL 与其主要靶标 SRC 之间显示出巨大的活性差异 (>950 倍差异)^[2]。

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

eCF506 显示出中等的口服生物利用度 (25.3%)。与未处理的动物对照相比，在用 eCF506 处理的小鼠的异种移植切片中观察到磷酸 SRC^Y416 显著减少^[2]。

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

515.66

C₂₆H₃₃D₅N₈O₃

1914078-41-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Fraser C, et al. Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase. J Med Chem. 2016 May 26;59(10):4697-710.  [Content Brief]

  [3]. Authors: Sweta Dash, et al. Preclinical efficacy of NXP900, a YES1/SRC kinase inhibitor in esophageal squamous cancer models. Journal of Clinical Oncology. Volume 41, Number 16_suppl.