BI-D1870

製品コードS2843 バッチS284301

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	C₁₉H₂₃F₂N₅O₂
	分子量	391.42	CAS No.	501437-28-1
Solubility (25°C)*	体外	DMSO	78 mg/mL (199.27 mM)
		Water	Insoluble
		Ethanol	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	BI-D1870 is an ATP-competitive inhibitor of S6 ribosome for RSK1/2/3/4 with IC50 of 31 nM/24 nM/18 nM/15 nM in cell-free assays, respectively; 10- to 100-fold selectivity for RSK than MST2, GSK-3β, MARK3, CK1 and Aurora B. BI-D1870 exhibits anticancer attributes including the generation of reactive oxygen species (ROS) and increases in endoplasmic reticulum (ER) stress and autophagy.
in vitro	BI-D1870 inhibits RSK1, RSK2, RSK3 and RSK4 with an IC50 of 10–30 nM, but does not significantly inhibit ten other AGC kinase members and over 40 other protein kinases tested at 100-fold higher concentrations. BI-D1870 is cell permeant and prevents the RSK-mediated phorbol ester- and EGF -induced phosphorylation of glycogen synthase kinase-3β and LKB1 in human embry-onic kidney 293 cells and Rat-2 cells. BI-D1870 does not affect the agonist-triggered phosphorylation of substrates for six other AGC kinases. Moreover, BI-D1870 does not suppress the phorbol ester- or EGF-induced phosphorylation of CREB. ^[1]

製品説明

BI-D1870 is an ATP-competitive inhibitor of S6 ribosome for RSK1/2/3/4 with IC50 of 31 nM/24 nM/18 nM/15 nM in cell-free assays, respectively; 10- to 100-fold selectivity for RSK than MST2, GSK-3β, MARK3, CK1 and Aurora B. BI-D1870 exhibits anticancer attributes including the generation of reactive oxygen species (ROS) and increases in endoplasmic reticulum (ER) stress and autophagy.

in vitro

BI-D1870 inhibits RSK1, RSK2, RSK3 and RSK4 with an IC50 of 10–30 nM, but does not significantly inhibit ten other AGC kinase members and over 40 other protein kinases tested at 100-fold higher concentrations. BI-D1870 is cell permeant and prevents the RSK-mediated phorbol ester- and EGF -induced phosphorylation of glycogen synthase kinase-3β and LKB1 in human embry-onic kidney 293 cells and Rat-2 cells. BI-D1870 does not affect the agonist-triggered phosphorylation of substrates for six other AGC kinases. Moreover, BI-D1870 does not suppress the phorbol ester- or EGF-induced phosphorylation of CREB. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Protein kinase assays
キナーゼアッセイ	Purified His6–RSK1, His6–RSK2 or GST–RSK2^{1–389:S381E} (1–2 units/mL) are assayed for 10 min at 30 °C in a 50 μL assay mixture in Buffer A containing 30 μM substrate peptide (KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK), 10 mM magnesium acetate and 100 μM of [γ-³²P]ATP. Reactions are terminated and analysed as described previously. The amount of enzyme that catalysed the phosphorylation of 1 nmol of substrate peptide in 1 min is termed one unit. In order to assay RSK and MSK1 in HEK-293 or Rat-2 cell lysates, these kinases are immunoprecipitated from the cell lysates (0.1 mg of lysate protein for RSK and 0.3 mg for MSK1) and for RSK assays the immunoprecipitates are washed twice with Buffer A containing 1 mM ATP and twice with Buffer A prior to the assay, as a precaution to ensure dissociation of BI-D1870 from the RSK isoforms.
細胞アッセイ	細胞株	Cell-free assays
	濃度	IC50 of 31, 24, 18 and 15 nM for RSK1, 2, 3, & 4, respectively.
	反応時間
	実験の流れ
動物実験	動物モデル	C57/BL6J mice
	投薬量	0.5 mg/kg
	投与方法	i.p.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Mol Cancer Ther, 2017, 16(5):793-804]

: Data from [Data independently produced by , , Sci Rep, 2016, 6:36134.]

: Data from [Data independently produced by , , Mol Cell Biol, 2014, 34(13): 2517-32]

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：

p90RSK pathway inhibition synergizes with cisplatin in TMEM16A overexpressing head and neck cancer [ BMC Cancer, 2024, 24(1):233]	PubMed: 38373988
The ribosomal protein S6 kinase alpha-1 (RPS6KA1) induces resistance to venetoclax/azacitidine in acute myeloid leukemia [ Leukemia, 2023, 37(8):1611-1625]	PubMed: 37414921
The ribosomal protein S6 kinase alpha-1 (RPS6KA1) induces resistance to venetoclax/azacitidine in acute myeloid leukemia [ Leukemia, 2023, 37(8):1611-1625]	PubMed: 37414921
Conjugated Bile Acids Promote Lymphangiogenesis by Modulation of the Reactive Oxygen Species-p90RSK-Vascular Endothelial Growth Factor Receptor 3 Pathway [ Cells, 2023, 12(4)526]	PubMed: 36831193
Control of cell state transitions [ Nature, 2022, 609(7929):975-985]	PubMed: 36104561
EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer [ Cell Rep, 2022, 41(11):111827]	PubMed: 36516759
IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR initiating a mesenchymal program in stromal, epithelial, and cancer cells [ iScience, 2022, 25(8):104806]	PubMed: 35992082
P90 ribosomal S6 kinase confers cancer cell survival by mediating checkpoint kinase 1 degradation in response to glucose stress [ Cancer Sci, 2022, 113(1):132-144]	PubMed: 34668620
p90RSK Regulates p53 Pathway by MDM2 Phosphorylation in Thyroid Tumors [ Cancers (Basel), 2022, 15(1)121]	PubMed: 36612117
Dual targeting of brain region-specific kinases potentiates neurological rescue in Spinocerebellar ataxia type 1 [ EMBO J, 2021, 40(7):e106106]	PubMed: 33709453

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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