WZ4002

製品コードS1173 バッチS117301

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H27ClN6O3
分子量 494.18 CAS No. 1213269-23-8
Solubility (25°C)* 体外 DMSO 13 mg/mL (26.3 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 WZ4002 is a novel, mutant-selective EGFR inhibitor for EGFR(L858R)/(T790M) with IC50 of 2 nM/8 nM in BaF3 cell line; does not inhibit ERBB2 phosphorylation (T798I).
in vitro WZ4002 inhibits other EGFR genotypes E746_A750 and E746_A750/T790M with IC50 of 2 and 6 nM. Besides, this compound suppresses widetype ERBB2 with an IC50 of 32 nM. It inhibits EGFR, AKT and ERK1/2 phosphorylation in NSCLC cell lines and prevents of EGFR phosphorylation in NIH-3T3 cells expressing different EGFR T790M mutant alleles. For this chemical, kinases that exhibited greater than 95% inhibition relative to the DMSO control at 10 μM are selected for measurement of their dissociation constants. This inhibitor, which possesses an ortho-methoxy group at the C2-aniline substituent, is more selective for EGFR compared to WZ3146. It is 100-fold less effective at inhibiting phosphorylation of WT EGFR compared to the quinazoline inhibitors. Similarly, this compound prevents EGFR kinase activity of recombinant L858R/T790M protein more potently than of WT EGFR, while the opposite is observed with HKI-272 and gefitinib. [1] In addition, the phosphorylated EGFR of Src TKI-resistant H1975 cells, as well as HCC827 cells, is completely suppressed by the third generation EGFR TKI, WZ4002. [2]
in vivo In a 2-week efficacy study, WZ4002 treatment results in significant tumor regressions compared to vehicle alone in both T790M containing murine models. [1] Treatment with low-dose of this compound, and high-dose of this compound leads to mean decreases in tracer uptake of 26%, and 36%, respectively. [3]

プロトコル(参考用のみ)

キナーゼアッセイ EGFR kinase assays
In vitro inhibitory enzyme kinetic assays using recombinant EGFR L858R/T790M and WT protein and are performed using the ATP/NADH coupled assay system in a 96-well format. WZ4002 is added to determine its inhibitory effects.
細胞アッセイ 細胞株 NSCLC, Ba/F3 cells, NIH-3T3 cells, PC9GR4 cells
濃度 0-1 μM
反応時間 72 hours
実験の流れ The NSCLC, Ba/F3 cells, NIH-3T3 cells, PC9GR4 cells are used and verified to contain EGFR delE746_A750/T790M by direct sequencing. Cell proliferation and growth assays are performed using the MTS assay. Site directed mutagenesis is performed using the Quick Change Site-Directed Mutagenesis kit.
動物実験 動物モデル EGFR-TL (T790M/L858R) mice
投薬量 25mg/kg
投与方法 Gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/20033049/
  • https://pubmed.ncbi.nlm.nih.gov/22157722/
  • https://pubmed.ncbi.nlm.nih.gov/22331221/

カスタマーフィードバック

Data from [Mol Cancer Ther, 2012, 11, 2149-57]

Data from [Lab Invest, 2011, 92, 371-383]

Data from [Lab Invest, 2011, 92, 371-383]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

RAB22A sorts epithelial growth factor receptor (EGFR) from early endosomes to recycling endosomes for microvesicles release [ J Extracell Vesicles, 2024, 13(7):e12494] PubMed: 39051763
ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors [ Cancer Metab, 2023, 11(1):20] PubMed: 37932830
MicroRNA-21 guide and passenger strand regulation of adenylosuccinate lyase-mediated purine metabolism promotes transition to an EGFR-TKI-tolerant persister state [ Cancer Gene Ther, 2022, 29(12):1878-1894] PubMed: 35840668
Extracellular vesicle drug occupancy enables real-time monitoring of targeted cancer therapy [ Nat Nanotechnol, 2021, 10.1038/s41565-021-00872-w] PubMed: 33686255
Non-Canonical Role of PDK1 as a Negative Regulator of Apoptosis through Macromolecular Complexes Assembly at the ER-Mitochondria Interface in Oncogene-Driven NSCLC [ Cancers (Basel), 2021, 13(16)4133] PubMed: 34439291
RAB31 marks and controls an ESCRT-independent exosome pathway [ Cell Res, 2020, 10.1038/s41422-020-00409-1] PubMed: 32958903
Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway [ Cancer Res, 2020, 80(21):4655-4667] PubMed: 32873635
Efficacy of the CDK7 Inhibitor on EMT-Associated Resistance to 3rd Generation EGFR-TKIs in Non-Small Cell Lung Cancer Cell Lines [ Cells, 2020, 9(12)E2596] PubMed: 33287368
HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. [ Nat Cell Biol, 2019, 21(8):1027-1040] PubMed: 31332347
Targeting FGFR overcomes EMT-mediated resistance in EGFR mutant non-small cell lung cancer. [ Oncogene, 2019, 38(37):6399-6413] PubMed: 31324888

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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