BIX-02565

Inhibitor of RPS6KA3

Structure

Information

  • RPS6KA3
  • Inhibitor
  • 20 nM

In Vitro Validations

Uniprot ID: P51812
Target Class: Protein kinase
Target SubClass: AGC
Potency: IC50
Potency Value: 1 nM
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: yes
Target aliases:
Ribosomal protein S6 kinase alpha-3, RSK2, MAPKAPK ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 LRRK2 16 nM, PRKD1 35 nM
Potency assay (off target): In a panel of 20 kinases, BIX-02565 inhibited six of them with IC50 < 1 uM. In an expanded panel of 20 kinases, BIX-02565 inhibited only 4 additional kinases with an IC50 < 1 uM (PRKD2, PRKD3, RET, FLT3). Overall, with the exceptions of LRRK2 and PRKD1, BIX-02565 is >100-fold selective for RPS6KA3 in vitro.
Probe Selectivity in Vitro:

Outside target family: Tested in a panel of 68 receptors, ion channels, and protein targets for off-target inhibition of radioligand binding @ 10 uM. The compound elicited >50% inhibition at adrenergic a1A-, a1B-, a1D-, a2A-, 2-, and imidazoline I2 receptors (IC50 values ranged between 0.052 and 1.820 uM).

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This compound is not recommended for use in vivo due to cardiotoxicity relating to its off-target effects on adrenergic receptors. Compounds with no off-target cardiotoxicity were later derived from this compound through additional medicinal chemistry. They would be more appropriate for use in vivo.

(last updated: 20 Mar 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

The compound has potential off-target activity on LRRK2 and PRKD1. The patent review (PMID: 27410995) describes how binding to the adrenergic receptors may result in a lethal decrease of heart rate which is also noted in the primary publications listed 10.1124/jpet.111.189365. Compound 15 in the same reference is offered as a better in vivo tool compound because it does not bind adrenergic receptors 10.1124/jpet.111.189365.

(last updated: 4 Aug 2021 )