Autotaxin (ATX) inhibitor | BI-2545

Target protein: 
ATX
Probe Name: 
BI-2545
MOLECULAR WEIGHT [DA]: 
527.4
In stock: 
41

Chemical structure

2D structure of BI-2545

Highlights

BI-2545 inhibits human ATX with an IC50 of 2.2 nM. In human whole blood BI-2545 inhibits Autotaxin with an IC50 of 29 nM and in rat whole blood with an IC50 of 96 nM.6 In vivo BI-2545 demonstrated after a single oral dose to rats at 10 mg/kg a LPA reduction of up to 90%. We also offer BI-3017 as inactive control.

3D structure of BI-2545

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Target information

Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). Recent studies suggest that the ATX-LPA axis is highly implicated in a number of pathophysiological diseases including inflammation, cancer and idiopathic pulmonary fibrosis.

BI-2545 bound to ATX (X-ray structure solved at Boehringer Ingelheim)

BI-2545 bound to ATX (X-ray structure solved at Boehringer Ingelheim)

In vitro Activity

In vitro activity table

Probe name / Negative control

BI-2545

BI-3017

MW [Da]

527.4

407.4

hATX LPA IC50 [nM]

2.2

8900

rat whole blood IC50 [nM]

96

n.d.

human whole blood (IC50) [nM]

29

n.d.

In vitro DMPK parameters

In vitro DMPK parameters table

Probe name

BI-2545

Solubility @ pH 6.8 [µg/ml]

<1

CACO permeability @ pH 7.4 [*10-6 cm/s]

9.32

CACO efflux ratio

1.41

Human hepatocyte clearance [%QH]

22

Plasma protein binding human [%]

n.d.

In vivo DMPK parameters

In vivo DMPK parameters table

Probe name

BI-2545

Rat PK (i.v.):

CL [mL/(min*kg)]

7

CL [%QH)]

10

MRT [h]

2.1

Vss [L/kg]

0.9

Rat PK (p.o.):

cmax [nM]

92

tmax [h]

1.7

MRT [h]

4.5

F [%]

30

Negative control

MOLECULAR WEIGHT OF NEGATIVE CONTROL [DA]: 
407.4

Chemical structure of the negative control BI-3017

Chemical structure of the negative control BI-3017

Selectivity

Selectivity data available

Probe name

BI-2545

Cerep®

Yes

Eurofins-Panlabs®

No

Invitrogen®

No

DiscoverX®

No

Dundee

No

Download selectivity data: 

Co-crystal structure of the BI probe compound and the target protein

The X-ray co-crystal structure of ATX with BI-2545 will be published (paper submitted).

reference molecules

See reference 1

Summary

BI-2545 inhibits human ATX with an IC50 of 2.2 nM. In human whole blood BI-2545 inhibits Autotaxin with an IC50 of 29 nM and in rat whole blood with an IC50 of 96 nM.

Supplementary data

References

  1. Discovery, Structure-Activity Relationship, and Binding Mode of an Imidazo[1,2-a]pyridine Series of Autotaxin Inhibitors

    Agnès Joncour et al.

    J. Med. Chem. 2017, 60, 6480-6515.

  2. Development of Autotaxin Inhibitors: An Overview of the Patent and Primary Literature

    Diana Castagna et al.

    J. Med. Chem. 2016, 59, 5604-5621.

  3. Autotaxin in the crosshairs: Taking aim at cancer and other inflammatory conditions

    Matthew G.K. Benesch, Yi M. Ko, Todd P.W. McMullen, David N. Brindley

    FEBS Letters, 2014, 588, 2712-2727.

  4. Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design

    Spencer B. Jones et al.

    ACS Med. Chem. Lett. 2016, 7, 857-861.

  5. Autotaxin: structure-function and signalling

    Anastassis Perrakis, Wouter H. Moolenaar

    J. Lipid Res. 2014, 55, 1010-1018.

  6. Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo ACS

    Christian A. Kuttruff, Marco Ferrara, Tom Bretschneider, Stefan Hoerer, Sandra Handschuh, Bernd Nosse, Helmut Romig, Paul Nicklin, and Gerald J. Roth

    Med. Chem. Lett. 2017