LGX818 (Encorafenib)

製品コードS7108 バッチS710802

印刷

化学情報

Chemical Structure Synonyms LGX818 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22 H27 Cl F N7 O4 S
分子量 540.01 CAS No. 1269440-17-6
Solubility (25°C)* 体外 DMSO 100 mg/mL (185.18 mM)
Ethanol 100 mg/mL (185.18 mM)
Water Insoluble
* <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 Encorafenib is a highly potent RAF inhibitor with selective anti-proliferative and apoptotic activity in cells expressing B-RAF(V600E) with EC50 of 4 nM. Phase 3.
in vitro

In the A375 (BRAFV600E) human melanoma cell line, Encorafenib (LGX818) suppresses phospho-ERK (EC50 = 3 nM) leading to potent inhibition of proliferation (EC50 = 4 nM). No significant activity is observed against a panel of 100 kinases (IC50 > 900 nM), and it does not inhibit proliferation of > 400 cell lines expressing wild-type BRAF. Contributing to the high potency of this compound is the extremely slow off-rate from BRAFV600E, which is not observed with other RAF inhibitors. In biochemical assays, the dissociation half-life is >24 hours, which translated into sustained target inhibition in cells following drug wash-out.

in vivo

Encorafenib (LGX818) is a potent and selective RAF kinase inhibitor with unique biochemical properties that contribute to an excellent pharmacological profile. Treatment with this compound at oral doses as low as 6 mg/kg resulted in strong (75%) and sustained (>24 hours) decrease in phospho-MEK, even following clearance of drug from circulation in single dose PK/PD studies in human melanoma xenograft models (BRAFV600E). It induces tumor regression in multiple BRAF mutant human tumor xenograft models grown in immune compromised mice and rats at doses as low as 1 mg/kg. Consistent with the in vitro data, it is inactive against BRAF wild-type tumors at doses up to 300 mg/kg bid, with good tolerability and linear increase in exposure. Efficacy is also achieved in a more disease-relevant spontaneous metastatic melanoma and a model of melanoma brain metastasis.

特徴 Orally bioavailable RAF-selective inhibitor.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 A375 cells
濃度 40 nM
反応時間 24 h
実験の流れ

Encorafenib (LGX818) was incubated with cells at different concentrations for 24 h.
動物実験 動物モデル Female nude mice bearing A375 (BRAF V600E) human melanoma tumor xenografts
投薬量 5 mg/kg
投与方法 Oral

参考

  • http://cancerres.aacrjournals.org/content/72/8_supplement/3790
  • https://pubmed.ncbi.nlm.nih.gov/28611198/

カスタマーフィードバック

, , Clin Cancer Res, 2017, 23(20):6203-6214

, , Cancer Lett, 2016, 370(2):332-44.

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：

Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases [ Cell Rep Med, 2025, 6(2):101943] PubMed: 39922199
HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAFV600E-mutant microsatellite stable colorectal cancer [ J Immunother Cancer, 2025, 13(1)e010460] PubMed: 39800382
Novel CDK2/CDK9 inhibitor fadraciclib targets cell survival and DNA damage pathways and synergizes with encorafenib in human colorectal cancer cells with BRAF(V600E) [ Oncogenesis, 2025, 14(1):27] PubMed: 40769976
Strong Hsp90α/β Protein Expression in Advanced Primary CRC Indicates Short Survival and Predicts Response to the Hsp90α/β-Specific Inhibitor Pimitespib [ Cells, 2025, 14(11)836] PubMed: 40498011
Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells [ Sci Rep, 2025, 15(1):2422] PubMed: 39827294
Adaptive Plasticity Tumor Cells Modulate MAPK-Targeting Therapy Response in Colorectal Cancer [ bioRxiv, 2025, 2025.01.22.634215] PubMed: 39896605
Ubiquitin-specific protease 22 controls melanoma metastasis and vulnerability to ferroptosis through targeting SIRT1/PTEN/PI3K signaling [ MedComm (2020), 2024, 5(8):e684] PubMed: 39135915
Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells [ Cell Rep, 2024, 43(9):114710] PubMed: 39240715
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] PubMed: 39319271
Combined RAF and MEK Inhibition to Treat Activated Non-V600 BRAF-Altered Advanced Cancers [ Oncologist, 2024, 29(1):15-24] PubMed: 37616543

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。