Tovorafenib (MLN2480)

製品コードS7121 バッチS712101

化学情報

	Synonyms	BIIB-024, TAK580, AMG-2112819, BSK1369, DAY-101	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₇H₁₂Cl₂F₃N₇O₂S
	分子量	506.29	CAS No.	1096708-71-2
Solubility (25°C)*	体外	DMSO	100 mg/mL (197.51 mM)
		Ethanol	100 mg/mL (197.51 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	Tovorafenib (MLN2480, BIIB-024, TAK580, AMG-2112819, BSK1369, DAY-101) is an oral, selective pan-Raf kinase inhibitor in chinical trials.
in vitro	MLN2480 inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preclinical cancer models at concentrations that are tolerated in vivo^[1]. It is found to activate phosphorylated MEK at very low concentrations, but inhibits this same activity at higher concentrations. The inhibitory effects of MLN-2480 are found to vary across models and genetic contexts^[2]. In vitro analysis of this drug combination of MLN2480 and TAK-733(an investigational allosteric MEK kinase inhibitor) in cell proliferation assays demonstrates synergistic activity .In addition, western blot analysis demonstrates the effect of MLN2480 in reversing feedback activation of MEK in response to TAK-733, leading to more concerted MAPK pathway inhibition.MLN-2480 only modestly inhibits PRAK^[1]^[2].
in vivo	In vivo, MLN2480 shows antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models^[3]. MLN-2480 (37.5 mg/kg) is well tolerated in a tumor xenograft model. The combination of MLN-2480 (12.5 mg) and TAK-733 (1 mg/kg) is effective in an SK-MEL-30 xenograft model, but monotherapy with either compound produces negligible effects^[2].

製品説明

Tovorafenib (MLN2480, BIIB-024, TAK580, AMG-2112819, BSK1369, DAY-101) is an oral, selective pan-Raf kinase inhibitor in chinical trials.

in vitro

MLN2480 inhibits MAPK pathway signaling in BRAF mutant and some RAS mutant preclinical cancer models at concentrations that are tolerated in vivo^[1].

It is found to activate phosphorylated MEK at very low concentrations, but inhibits this same activity at higher concentrations. The inhibitory effects of MLN-2480 are found to vary across models and genetic contexts^[2].

In vitro analysis of this drug combination of MLN2480 and TAK-733(an investigational allosteric MEK kinase inhibitor) in cell proliferation assays demonstrates synergistic activity .In addition, western blot analysis demonstrates the effect of MLN2480 in reversing feedback activation of MEK in response to TAK-733, leading to more concerted MAPK pathway inhibition.MLN-2480 only modestly inhibits PRAK^[1]^[2].

in vivo

In vivo, MLN2480 shows antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models^[3].

MLN-2480 (37.5 mg/kg) is well tolerated in a tumor xenograft model. The combination of MLN-2480 (12.5 mg) and TAK-733 (1 mg/kg) is effective in an SK-MEL-30 xenograft model, but monotherapy with either compound produces negligible effects^[2].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	DKFZ-BT66 cells
	濃度
	反応時間	24 h
	実験の流れ	Cells were treated for 24 hours with the indicated inhibitors before lysis.
動物実験	動物モデル	C57BL/6J mice
	投薬量	12.5 mg/kg
	投与方法	oral gavage

参考

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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
Anti-tumor activity of the pan-RAF inhibitor TAK-580 in combination with KPT-330 (selinexor) in multiple myeloma [ Int J Hematol, 2021, 10.1007/s12185-021-03244-1]	PubMed: 34741230
Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses. [ Cell Rep, 2019, 29(3):573-588]	PubMed: 31618628
Development of Highly Sensitive Biosensors of RAF Dimerization in Cells. [ Sci Rep, 2019, 9(1):636]	PubMed: 30679688
Comparative analysis of the phototoxicity induced by BRAF inhibitors and alleviation through antioxidants. [ Photodermatol Photoimmunol Photomed, 2019, 10.1111/phpp.12520]	PubMed: 31618797
Establishment and application of a novel patient-derived KIAA1549:BRAF-driven pediatric pilocytic astrocytoma model for preclinical drug testing [ Oncotarget, 2017, 8(7):11460-11479]	PubMed: 28002790

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。