Encorafenib

製品コードS7108 バッチS710801

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 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 LGX818 does not inhibit proliferation of > 400 cell lines expressing wild-type BRAF. Contributing to the high potency of LGX818 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. [1]
in vivo

LGX818 treatment 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). LGX818 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, LGX818 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. LGX818 is a potent and selective RAF kinase inhibitor with unique biochemical properties that contribute to an excellent pharmacological profile. [1]
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

Different concentrations of encorafenib were incubated with cells 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

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：

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
Combined RAF and MEK Inhibition to Treat Activated Non-V600 BRAF-Altered Advanced Cancers [ Oncologist, 2024, 29(1):15-24] PubMed: 37616543
Neratinib, a pan ERBB/HER inhibitor, restores sensitivity of PTEN-null, BRAFV600E melanoma to BRAF/MEK inhibition [ Front Oncol, 2024, 14:1191217] PubMed: 38854737
CDK4/6 inhibition to resensitize BRAF/EGFR inhibitor in patient-derived BRAF/PTEN-mutant colon cancer cells [ Transl Cancer Res, 2024, 13(7):3695-3703] PubMed: 39145064
A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAFV600E colorectal tumors [ Nat Cancer, 2023, 4(2):240-256] PubMed: 36759733
High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer [ Mol Cancer Ther, 2023, 22(2):227-239] PubMed: 36442478
A Combination of Conformation-Specific RAF Inhibitors Overcome Drug Resistance Brought about by RAF Overexpression [ Biomolecules, 2023, 13(8)1212] PubMed: 37627277
USP10 Regulates ZEB1 Ubiquitination and Protein Stability to Inhibit ZEB1-Mediated Colorectal Cancer Metastasis [ Mol Cancer Res, 2023, 21(6):578-590] PubMed: 36940483
BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability [ Sci Adv, 2023, 9(35):eade7486] PubMed: 37656784
Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation [ J Hematol Oncol, 2022, 15(1):109] PubMed: 35978321

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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