Cobimetinib (GDC-0973)

製品コードS8041 バッチS804103

化学情報

	Synonyms	RG7420,XL518	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₁H₂₁F₃IN₃O₂
	分子量	531.31	CAS No.	934660-93-2
Solubility (25°C)*	体外	DMSO	100 mg/mL (188.21 mM)
		Ethanol	50 mg/mL warmed with 50ºC water bath (94.1 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	Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing more than 100-fold selectively for MEK1 over MEK2 and showed no significant inhibition when tested against a panel of more than 100 of serine-threonine and tyrosine kinases. Cobimetinib induces apoptosis. Phase 3.
in vitro	Cobimetinib shows strong activity on cell growth inhibtion in a broad panel of tumor types, particularly in BRAF or KRAS mutant cancer cell lines. In combination with GDC-0941, GDC-0973 results in reduced viability, pathway inhibition, and increased apoptosis in 888MEL and A2058 cells. ^[1] Coadministration of GDC-0973 and vemurafenib significantly increases decreased levels of GLUT-1 on the cellular membrane across all BRAFV600E lines. ^[2]
in vivo	In mice bearing BRAFV600E and KRAS mutant tumors, Cobimetinib (10 mg/kg, p.o.) produces antitumor efficacy, and the combination of GDC-0973 and GDC-0941 show improved efficacy. ^[1] In mice bearing drug-resistant A375 xenografts, combination of GDC-0973 and GDC-0941 induces decreased levels of hexokinase II, c-RAF, Ksr and p-MEK protein. ^[2]

製品説明

Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing more than 100-fold selectively for MEK1 over MEK2 and showed no significant inhibition when tested against a panel of more than 100 of serine-threonine and tyrosine kinases. Cobimetinib induces apoptosis. Phase 3.

in vitro

Cobimetinib shows strong activity on cell growth inhibtion in a broad panel of tumor types, particularly in BRAF or KRAS mutant cancer cell lines. In combination with GDC-0941, GDC-0973 results in reduced viability, pathway inhibition, and increased apoptosis in 888MEL and A2058 cells. ^[1]

Coadministration of GDC-0973 and vemurafenib significantly increases decreased levels of GLUT-1 on the cellular membrane across all BRAFV600E lines. ^[2]

in vivo

In mice bearing BRAFV600E and KRAS mutant tumors, Cobimetinib (10 mg/kg, p.o.) produces antitumor efficacy, and the combination of GDC-0973 and GDC-0941 show improved efficacy. ^[1]

In mice bearing drug-resistant A375 xenografts, combination of GDC-0973 and GDC-0941 induces decreased levels of hexokinase II, c-RAF, Ksr and p-MEK protein. ^[2]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	H2122 cells
	濃度	4.2 nM
	反応時間
	実験の流れ	Cells were treated with different concentrations of GDC0973 (MEKi) either alone or with PI3K inhibitor (GDC-0941) and assayed for cell death using a Nucleasomal ELISA assay.
動物実験	動物モデル	Molm-13, Molm-16, MX-1, DLD-1, HCT-116, LoVo, FaDu, 537MEL, A2058, A2058-X1, A375, A375.X1, A427, A549, Calu-6, EBC-1, NCI-H441, NCI-H2122, NCI-H460, NCI-H520.X1, SKOV-3, KP4-X1.1, MiaPaCa-2, 22Rv1, DU-145.X1,S, NCI-H69 xenograft tumors in mice
	投薬量	10 mg/kg
	投与方法	p.o.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Mol Cell Proteomics, 2017, 16(2):265-277]

: Data from [Data independently produced by , , Cell Physiol Biochem, 2018, 47(2):680-693]

: Data from [Data independently produced by , , PLoS One, 2017, 12(11):e0186981]

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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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