(2R)-2,4-ジメチルピペラジン-1-カルボン酸(4-(2-フルオロ-3-クロロアニリノ)-7-メトキシキナゾリン-6-イル)

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Warning

• 危険有害性情報

  H302：飲み込むと有害

  H315：皮膚刺激

  H319：強い眼刺激

  H335：呼吸器への刺激のおそれ

• 注意書き

  P261：粉じん/煙/ガス/ミスト/蒸気/スプレーの吸入を避ける こと。

  P305+P351+P338：眼に入った場合：水で数分間注意深く洗うこと。次にコ ンタクトレンズを着用していて容易に外せる場合は外す こと。その後も洗浄を続けること。

(2R)-2,4-ジメチルピペラジン-1-カルボン酸(4-(2-フルオロ-3-クロロアニリノ)-7-メトキシキナゾリン-6-イル) 化学特性,用途語,生産方法

• 説明

  AZD3759 is an EGFP inhibitor (Epidermal growth factor receptor tyrosine kinase inhibitor) with blood brain barrier (BBB) penetration. It has the potential for the treatment of non-small cell lung cancer (NSCLC), with brain metastases (BM) and leptomengingeal metastases (LM) since this type of cancer often contain a lot of activating mutations of the epidermal growth factor receptor (EGFR). It has excellent capability of penetrating the blood brain barrier to reach the central nervous system.

• 生物活性

  AZD3759 is a new, potent, oral, active central nervous system (CNS)‐penetrant EGFR inhibitor. It is mainly designed to effectively bypass the blood-brain barrier to address CNS metastasis in NSCLC patients carrying EGFR mutations, such as brain metastasis (BM) and dura mater (or pia mater, leptomeningeal metastases). AZD3759 is currently at a phase I/II research and development stage. At Km ATP concentrations, the half maximal inhibitory concentrations (IC50) were 0.3, 0.2, and 0.2 nM for wild‐type EGFR and mutated variants L858R and exon19Del, respectively. AZD3759 exhibited inhibitory effects on the proliferation of the phosphorylated (p) EGFR pathway and EGFR mutant-derived PC‐9 and H3255 cells, with IC50 of 7.7 nm and 7 nm, respectively. However, it had no inhibitory effect on the proliferation rate of H838 cells[4].

• 参考文献

  [1] Zeng, Qingbei, et al. "Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)." Journal of Medicinal Chemistry 58.20(2015):8200.
  [2] Yang, Zhenfan, et al. "Abstract LB-217: Antitumor activities of AZD3759, a novel EGFR inhibitor with excellent penetration across central nervous system (CNS), in preclinical animal models." Cancer Research 76.14 Supplement(2016):LB-217-LB-217.
  [3] Xiong, S., et al. "Determination of AZD3759 in rat plasma and brain tissue by LC-MS/MS and its application in pharmacokinetic and brain distribution studies." Journal of Pharmaceutical & Biomedical Analysis140(2017):362-366.
  [4] Qingjun Wu. “Determination and pharmacokinetic study of AZD-3759 in rat plasma by ultra performance liquid chromatography with triple quadrupole mass spectrometer.” Thoracic Cancer 9 11 (2018): 1383–1389.

(2R)-2,4-ジメチルピペラジン-1-カルボン酸(4-(2-フルオロ-3-クロロアニリノ)-7-メトキシキナゾリン-6-イル) 生産企業

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(2R)-2,4-ジメチルピペラジン-1-カルボン酸(4-(2-フルオロ-3-クロロアニリノ)-7-メトキシキナゾリン-6-イル) スペクトルデータ(¹HNMR)

1626387-80-1, (2R)-2,4-ジメチルピペラジン-1-カルボン酸(4-(2-フルオロ-3-クロロアニリノ)-7-メトキシキナゾリン-6-イル) キーワード