Lifirafenib (BGB-283)

製品コードS7926 バッチS792601

印刷

化学情報

Synonyms

Beigene-283

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₅H₁₇F₃N₄O₃

分子量

478.42

CAS No.

1446090-79-4

Solubility (25°C)*

体外

DMSO

95 mg/mL (198.57 mM)

Ethanol

95 mg/mL (198.57 mM)

Water

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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.300mg/ml (4.81mM)	Taking the 1 mL working solution as an example, add 50 μL of 46 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.790mg/ml (1.65mM)	Taking the 1 mL working solution as an example, add 50 μL of 15.8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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	Lifirafenib (BGB-283, Beigene-283) は、生化学的アッセイにおいて、組換えBRAFV600Eキナーゼドメイン、EGFRおよびEGFR T790M/L858R変異体に対し、23、29および495 nMのIC50値でRAFファミリーキナーゼおよびEGFR活性を強力に阻害します。
in vitro	Lifirafenib (BGB-283) potently inhibits BRAFV600E-activated ERK phosphorylation and cell proliferation in vitro. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harboring BRAFV600E and EGFR mutation/amplification. In BRAFV600E colorectal cancer cell lines, this compound effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation. It demonstrates selective cytotoxicity to cell lines harboring BRAFV600E or EGFR mutations. In A431 cells, it inhibits the EGF-induced EGFR autophosphorylation on Tyr1068 in a dose-dependent manner. In WiDr colorectal cancer cells, it is shown to be able to inhibit the feedback activation of EGFR signaling and achieves sustained inhibition of pERK.
in vivo	Lifirafenib (BGB-283) treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell line-derived and primary human colorectal tumor xenografts bearing BRAFV600E mutation. It is highly efficacious in BRAF(V600E) colorectal cancer xenograft models, including HT29, Colo205, and two primary tumor xenografts harboring BRAFV600E mutation. In addition, this compound shows compelling efficacy in a WiDr xenograft model where EGFR reactivation is shown to be induced upon BRAF inhibition. It induces tumor regression in HCC827 but not in A431 xenograft. BGB-283 inhibits phosphorylation of both ERK1/2 and EGFR and displays potent antitumor activity in WiDr tumor xenografts. It potently inhibits MEK and ERK phosphorylation and DUSP6 expression in vivo when dosed repeatedly. There is no detectable difference on AKT phosphorylation.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	A375 cells
	濃度	0.03, 1, 10 μM
	反応時間	3 days
	実験の流れ	The number of cells seeded per well of a 96-well plate is optimized for each cell line to ensure logarithmic growth over the 3 days treatment period. Cells are left to attach for 16 hours and then treated with a 10-point dilution series of Lifirafenib (BGB-283) in duplicate. Following a 3-day exposure to the compound, a volume of CellTiter-Glo reagent equal to the volume of cell culture medium present in each well is added. Mixture is mixed on an orbital shaker for 2 minutes to allow cell lysing, followed by 10 minutes incubation at room temperature to allow development and stabilization of luminescent signal. Luminescent signal is measured
動物実験	動物モデル	NOD/SCID and BALB/c nude mice
	投薬量	2.5 to 30 mg/kg
	投与方法	p.o.

参考

https://pubmed.ncbi.nlm.nih.gov/26208524/

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：

BRAFΔβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability [ Sci Adv, 2023, 9(35):eade7486]	PubMed: 37656784
NOTCH signaling limits the response of Low Grade Serous Ovarian Cancers to MEK inhibition [ Mol Cancer Ther, 2022, MCT-22-0004]	PubMed: 36198031
Multiple Low Dose Therapy as an Effective Strategy to Treat EGFR Inhibitor-Resistant NSCLC Tumours [ Nat Commun, 2020, 11(1):3157]	PubMed: 32572029
Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers [ Cell Rep, 2020, 31(11):107764]	PubMed: 32553168
Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses. [ Cell Rep, 2019, 29(3):573-588]	PubMed: 31618628
A novel anti-melanoma SRC-family kinase inhibitor. [ Oncotarget, 2019, 10(23):2237-2251]	PubMed: 31040916

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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