LY3214996 (Temuterkib)

製品コードS8534 バッチS853402

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₂₇N₇O₂S
	分子量	453.56	CAS No.	1951483-29-6
Solubility (25°C)*	体外	DMSO	27.5 mg/mL (60.63 mM)
		Ethanol	15 mg/mL (33.07 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	Temuterkib (LY3214996) は、IC50 が 5 nM の選択的かつ新規のERK1/2阻害剤であり、生化学アッセイで両方の酵素に作用します。BRAF および RAS 変異がん細胞株において、細胞内 phospho-RSK1 を強力に阻害します。
in vitro	Temuterkib (LY3214996) possesses an optimal balance of potency (hERK1 IC50 5 nM, hERK2 IC50 5nM, pRSK IC50 0.43 µM) and solubility. In an unbiased tumor cell panel sensitivity profiling for inhibition of cell proliferation, tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation are generally sensitivity to this compound.
in vivo	In tumor xenograft models, Temuterkib (LY3214996) inhibits PD biomarker phospho-p90RSK1 in tumors and the PD effects are correlated with compound exposures and anti-tumor activities. It shows either similar or superior anti-tumor activity as compared to other published ERK inhibitors in BRAF or RAS mutant cell lines and xenograft models. Oral administration of this compound as a single agent significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models. In addition, it has anti-tumor activity in a A375 melanoma xenograft model due to MAPK reactivation, may have potential for treatment of melanoma patients who have failed BRAF therapies. More importantly, it can be combined with investigational and approved agents in preclinical models, particularly KRAS mutant models. Combination treatment with a CDK4/6 inhibitor is well tolerated and results in potent tumor growth inhibition or regression in multiple in vivo cancer models, including KRAS mutant colorectal and non-small cell lung cancers. This compound has good PK properties (dog, AUCoral 23800 nM*hr, CL 12.1 mL/min/kg, bioavailability 75.4%), IVTI (TED50 =16 mg/kg pRSK1) and demonstrates significant in vivo efficacy in several human cancer xenograft models.

製品説明

Temuterkib (LY3214996) は、IC50 が 5 nM の選択的かつ新規のERK1/2阻害剤であり、生化学アッセイで両方の酵素に作用します。BRAF および RAS 変異がん細胞株において、細胞内 phospho-RSK1 を強力に阻害します。

in vitro

Temuterkib (LY3214996) possesses an optimal balance of potency (hERK1 IC50 5 nM, hERK2 IC50 5nM, pRSK IC50 0.43 µM) and solubility. In an unbiased tumor cell panel sensitivity profiling for inhibition of cell proliferation, tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation are generally sensitivity to this compound.

in vivo

In tumor xenograft models, Temuterkib (LY3214996) inhibits PD biomarker phospho-p90RSK1 in tumors and the PD effects are correlated with compound exposures and anti-tumor activities. It shows either similar or superior anti-tumor activity as compared to other published ERK inhibitors in BRAF or RAS mutant cell lines and xenograft models. Oral administration of this compound as a single agent significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models. In addition, it has anti-tumor activity in a A375 melanoma xenograft model due to MAPK reactivation, may have potential for treatment of melanoma patients who have failed BRAF therapies. More importantly, it can be combined with investigational and approved agents in preclinical models, particularly KRAS mutant models. Combination treatment with a CDK4/6 inhibitor is well tolerated and results in potent tumor growth inhibition or regression in multiple in vivo cancer models, including KRAS mutant colorectal and non-small cell lung cancers.

This compound has good PK properties (dog, AUCoral 23800 nM*hr, CL 12.1 mL/min/kg, bioavailability 75.4%), IVTI (TED50 =16 mg/kg pRSK1) and demonstrates significant in vivo efficacy in several human cancer xenograft models.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	A375 cells
	濃度	1 μM
	反応時間
	実験の流れ	Cells were treated with various concentrations of Temuterkib (LY3214996).
動物実験	動物モデル	NSG mice
	投薬量	100 mg/kg
	投与方法	o.g.

参考

http://cancerres.aacrjournals.org/content/77/13_Supplement/4973
https://www.researchgate.net/publication/318810417
https://pubmed.ncbi.nlm.nih.gov/35764642/

https://pubmed.ncbi.nlm.nih.gov/36384095/

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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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