| Chemical Properties | Back Directory | [Boiling point ]
668.9±55.0 °C(Predicted) | [density ]
1.513±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 250 mg/mL (474.01 mM) | [form ]
A solid | [pka]
7.46±0.40(Predicted) | [color ]
Off-white to light yellow | [InChIKey]
ZDOBSAPHUUUOHX-OSYLJGHBSA-N | [SMILES]
O=C(N1C[C@]2([H])[C@@H](CNC(C3=CC=C(NN=N4)C4=C3)=O)[C@]2([H])C1)OCC5=CC(C(F)(F)F)=CC(C(F)(F)F)=C5 |
| Hazard Information | Back Directory | [Uses]
BI-2545 is a potent autotaxin (ATX) inhibitor that significantly reduces LPA, with IC50s of 2.2 nM and 3.4 nM for human ATX and rat ATX, respectively[1]. | [Biological Activity]
BI-2545 is a PF-8380 structure analog with improved autotaxin (ATX; ENPP2) inhibitory potency (human/r at ATX IC50 = 2.2/3.4 nMIC50 = 29/96 nM using human/r at whole blood (WB); human ATX/r at ATX/r at WB IC50 = 6.5/13/307 nM with PF-8380)in vivo pharmacokinetic profileoral availabilityand lysophosphatidic acid (LPA)-lowering efficacy (BI-2545 Cmax/AUC/T1/2/Max 18:2 LPA reduction = 140 nM/675 nM?h/3.4 h/90.4% post 10 mg/kg p.o. in rats vs. 60.3 nM/342 nM?h/2.5 h/32.2% with PF-8380). BI-2545 exhibits no hERG inhibitory activity (IC50 >10 μM vs. 480 nM with PF-8380) and displays significant cross-reactivity towards only 4 targets among a panel of 48 enzymes/receptors/transporters/channel proteins at a high concentration of 10 μM (55%80%66%61% inhibtion of 5-HT2aL-type Calcium channelNa+ channel site 2and norepinephrine transporterrespectively). | [in vivo]
BI-2545 (10 mg/kg; p.o.) has high and sustained in vivo efficacy in reducing LPAs[1].
BI-2545 (10 mg/kg; p.o.) has a half-life of t1/2=3.4 hours[1].
| Animal Model: | Rat[1] | | Dosage: | 10 mg/kg | | Administration: | Oral administration | | Result: | Reduces the sum of the plasma LPA species up to 90%. |
| [IC 50]
Autotaxin | [References]
[1] Kuttruff, C. A., et al. Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo. ACS Medicinal Chemistry Letters, 8(12), 1252–1257. |
|
|