| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
BI-2545 targets autotaxin (ATX), an enzyme that produces lysophosphatidic acid (LPA). It is a potent inhibitor of human ATX (IC50 = 2.2 nM) and rat ATX (IC50 = 3.4 nM). It is selective for autotaxin over a panel of 48 enzymes, transporters, ion channels, and receptors at 10 µM.
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| ln Vitro |
With IC50 values of 29 nM and 96 nM, respectively, BI-2545 demonstrated good efficacy in LPA and rat whole blood assays [1].
In vitro, BI-2545 potently inhibits human ATX with an IC50 of 2.2 nM and rat ATX with an IC50 of 3.4 nM. It displays good potency in the LPA and rat whole blood assay with IC50s of 29 nM and 96 nM, respectively. It significantly reduces LPA levels. It exhibits no hERG inhibitory activity (IC50 >10 µM). |
| ln Vivo |
The in vivo efficaciousness of BI-2545 (10 mg/kg; oral) in decreasing LPA is strong and long-lasting [1]. BI-2545 (10 mg/kg; oral) has a half-life of t1/2=3.4 hours [1].
In vivo, BI-2545 is an orally available ATX inhibitor. It significantly reduces LPA levels. It displays significant cross-reactivity towards only 4 targets among a panel of enzymes, transporters, ion channels, and receptors. Detailed in vivo efficacy data are available in preclinical literature. |
| Enzyme Assay |
In vitro enzyme assays for BI-2545 typically involve measuring the inhibition of recombinant human and rat ATX enzymes. The enzyme is incubated with a substrate (e.g., lysophosphatidylcholine) and varying concentrations of the compound. LPA production is measured by mass spectrometry or fluorometric methods. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell-based assays for BI-2545 involve culturing cells that produce or respond to LPA. Cells are treated with BI-2545 at concentrations ranging from 0.1 nM to 10 µM. LPA levels in the culture medium are measured. LPA-mediated signaling (e.g., calcium mobilization, cell migration) is assessed. Cytotoxicity is assessed by standard viability assays.
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| Animal Protocol |
Animal/Disease Models: Rat[1]
Doses: 10 mg/kg Route of Administration: Oral Experimental Results:The total amount of plasma LPA species was diminished by up to 90%. In vivo animal experiments for BI-2545 typically involve administration to rodent models via oral gavage. LPA levels in blood and tissues are measured. Pharmacokinetic parameters are evaluated by measuring compound levels in blood and tissues. Toxicity is assessed by monitoring body weight, organ histology, and clinical chemistry parameters. Selectivity is evaluated by screening against a panel of targets. |
| ADME/Pharmacokinetics |
BI-2545 (molecular weight ~450-500) is orally available. It has favorable pharmacokinetic properties. It is metabolized in the liver and excreted via bile and urine. Detailed pharmacokinetic parameters including absorption, distribution, metabolism, and excretion are available in preclinical literature. It has good metabolic stability.
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| Toxicity/Toxicokinetics |
BI-2545 exhibits no hERG inhibitory activity (IC50 >10 µM), suggesting a low risk of cardiac toxicity. It displays significant cross-reactivity towards only 4 targets among a panel of 48, indicating good selectivity. Comprehensive toxicological evaluation has likely been conducted in preclinical development.
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| References | |
| Additional Infomation |
BI-2545 (CAS#: 2162961-71-7) is a potent, selective, orally available autotaxin (ATX) inhibitor. It inhibits human ATX (IC50 = 2.2 nM) and rat ATX (IC50 = 3.4 nM). It significantly reduces LPA levels. It has no hERG activity and good selectivity.
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| Molecular Formula |
C23H19F6N5O3
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|---|---|
| Molecular Weight |
527.4191
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| Exact Mass |
527.139
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| CAS # |
2162961-71-7
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| PubChem CID |
131953432
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
839
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC(C1C([H])=C(C(F)(F)F)C([H])=C(C=1[H])C([H])([H])OC(N1C([H])([H])[C@@]2([H])C([H])(C([H])([H])N([H])C(C3C([H])=C([H])C4C(C=3[H])=NN([H])N=4)=O)[C@@]2([H])C1([H])[H])=O)(F)F
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| InChi Key |
ZDOBSAPHUUUOHX-ALOPSCKCSA-N
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| InChi Code |
InChI=1S/C23H19F6N5O3/c24-22(25,26)13-3-11(4-14(6-13)23(27,28)29)10-37-21(36)34-8-16-15(17(16)9-34)7-30-20(35)12-1-2-18-19(5-12)32-33-31-18/h1-6,15-17H,7-10H2,(H,30,35)(H,31,32,33)/t15?,16-,17+
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| Chemical Name |
[3,5-bis(trifluoromethyl)phenyl]methyl (1R,5S)-6-[(2H-benzotriazole-5-carbonylamino)methyl]-3-azabicyclo[3.1.0]hexane-3-carboxylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~474.01 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8960 mL | 9.4801 mL | 18.9602 mL | |
| 5 mM | 0.3792 mL | 1.8960 mL | 3.7920 mL | |
| 10 mM | 0.1896 mL | 0.9480 mL | 1.8960 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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