BI-D1870

Catalog No.S2843

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.

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BI-D1870 Chemical Structure

BI-D1870 Chemical Structure
Molecular Weight: 391.42

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Related Compound Libraries

BI-D1870 is available in the following compound libraries:

Product Information

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  • Research Area

Product Description

Biological Activity

Description 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.
Targets RSK4 [1]
(Cell-free assay)
RSK3 [1]
(Cell-free assay)
RSK2 [1]
(Cell-free assay)
RSK1 [1]
(Cell-free assay)
IC50 15 nM 18 nM 24 nM 31 nM
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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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... Click to View More Cell Line Experimental Data

In vivo
Features

Protocol(Only for Reference)

Kinase Assay: [2]

Protein kinase assays 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] GP Sapkota, et al. Biochem J, 2007, 401(Pt 1), 29–38.

Chemical Information

Download BI-D1870 SDF
Molecular Weight (MW) 391.42
Formula

C19H23F2N5O2

CAS No. 501437-28-1
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 78 mg/mL (199.27 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <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.
Chemical Name 6(5H)-Pteridinone, 2-[(3,5-difluoro-4-hydroxyphenyl)amino]-7,8-dihydro-5,7-dimethyl-8-(3-methylbutyl)-

Customer Product Validation(2)


Click to enlarge
Rating
Source Mol Cell Biol, 2014, 34(13): 2517-32. BI-D1870 purchased from Selleck
Method Western Blot
Cell Lines HeLa cells
Concentrations 10 μM
Incubation Time 3 h
Results BI-D1870 alone also reduced insulin-induced eIF4B S422 phosphorylation. Meanwhile, although rapamycin alone did not inhibit the eIF4B S422 phosphorylation, its combination with U0126 or BI-D1870 did.

Click to enlarge
Rating
Source J Biol Chem, 2014, 289(46): 31950-9. BI-D1870 purchased from Selleck
Method Western Blot
Cell Lines N41/OX1R cells
Concentrations 1 μM 、10 μM
Incubation Time 1 h
Results BI-D1870 enhanced phosphorylation of RSK, but did not affect the orexin-stimulated mTORC1 activation.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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