BI-D1870

Catalog No.S2843 Batch:S284302

Technical Data

Formula

C₁₉H₂₃F₂N₅O₂

Molecular Weight

391.42

CAS No.

501437-28-1

Solubility (25°C)*

In vitro

DMSO

78 mg/mL (199.27 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

1.25mg/ml

Taking the 1 mL working solution as an example, add 50 μL 25 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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. BI-D1870 exhibits anticancer attributes including the generation of reactive oxygen species (ROS) and increases in endoplasmic reticulum (ER) stress and autophagy.

Targets

RSK4 ^[1] (Cell-free assay)	RSK3 ^[1] (Cell-free assay)	RSK2 ^[1] (Cell-free assay)	RSK1 ^[1] (Cell-free assay)
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]

Protocol (from 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.
Animal Study:^{^[3]}	Animal Models C57/BL6J mice Dosages 0.5 mg/kg Administration i.p.

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.

Animal Study:^{^[3]}

Animal Models
C57/BL6J mice
Dosages
0.5 mg/kg
Administration
i.p.

References

Customer Product Validation

: 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]

: Data from [Data independently produced by , , J Biol Chem, 2014, 289(46): 31950-9]

Selleck's BI-D1870 has been cited by 55 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.