BI-D1870

Protein target name:

RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6

Mechanism of action:

ATP-competitive inhibitor

Recommended Concentration for use in cells:

10-1,000 nM

Probe Availability

MedChem Express (501437-28-1)

Cayman (501437-28-1)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

AGC

HUGO ID:

HGNC:10430 HGNC:10431 HGNC:10432 HGNC:10435

Entrez gene ID:

6195 6196 6197 27330

UNIPROT ID:

Q15418 Q15349 P51812 Q9UK32

Target alias:

RSK1, RSK2, RSK3, RSK4

Probe Details

Chemical Probes Portal ID:

CPP108

PubChem CID:

25023738

ChEMBL ID:

CHEMBL573107

SMILES string:

CC1C(=O)N(C2=CN=C(N=C2N1CCC(C)C)NC3=CC(=C(C(=C3)F)O)F)C

InChi Key:

DTEKTGDVSARYDS-UHFFFAOYSA-N

Orthogonal probe:

LJI308BIX-02565

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

31 nM RPS6KA1

Potency assay:

RPS6KA3 24 nM, RPS6KA2 18 nM; RPS6KA6 15 nM

Off target activity

Potency (off target):

IC50

Off target protein and potency:

MST2 0.86 uMGSK3 beta 1.59 uMMARK3 2.20 uMCSNK2A1 0.45 uMAURKB 0.34 uMPLK1 0.10 uM

Potency assay (off target):

BI-D1870 showed little activity against 50 off-target kinases in vitro

In cell validation

On target activity in cells

Potency in cells:

IC50

1 uM

Potency assay (cells):

In HEK-293 cells, BI-D1870 inhibited phosphorylation of RPS6KA protein substrates but not those for several off-target kinases

Target engagement assay (cells):

Indirect: inhibition of protein substrate phosphorylation

Primary Reference

Reference (doi):

10.1042/BJ20061088

Reference (PMID):

17040210

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

Although the initial paper was excellent, and many studies have used this compound to uncover interesting biology, more data has come to light recently. A recent paper discloses a new RSK inhibitor, and they collected data that shows BI-D1870 has more off target kinase activities than a best in class chemical probe should have. This extra information can be found in the supplemental material from this paper: http://www.ncbi.nlm.nih.gov/pubmed/24554780. LJI308 may be more suitable as a probe for the RSKs. In my own work I would likely use them both. Another paper points out that many scientists use BI-D1870 at high concentrations (10 uM), and when used side by side with another RSK compound (SL0101), different results emerge in different systems, suggesting off target activities. This paper is found here: http://www.ncbi.nlm.nih.gov/pubmed/25889895. This compound may be useful for exploration of RSK biology in some contexts if used carefully (lower concentrations), but recent work has demonstrated that it completely inhibits quite a few kinases in vitro at 10 uM. These results complicate its use as a chemical probe and means more experiments need to be done to understand the involvement of the RSKs in the biological process in question. If BI-D1870 is used in a cellular assay, the concentration should be kept lower than 1 uM or multiple kinases will be inhibited. One should also use other inhibitors such as LJI308, and target knockdown to validate findings.

Jun 12 2016 - 3:12am

I agree with the previously posted comments. In addition to LJI308, analog LJH685 has been co-crystallized with RPS6KA3 N-terminal domain (pdb 4nus). However, commercial availability is unknown as of this date.

Jun 21 2016 - 11:52am

BI-D1870

Probe Availability

Probe Information

Target Details

RSK1, RSK2, RSK3, RSK4

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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BI-D1870

Probe Availability

Probe Information

Target Details

RSK1, RSK2, RSK3, RSK4

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?