(S)-BI 665915
(S)-BI 665915 is an orally active oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitor with an IC50 of 1.7 nM for FLAP binding. (S)-BI 665915 inhibits FLAP functional in human whole blood with an IC50 of 45 nM. (S)-BI 665915 demonstrates an excellent cross-species agent metabolism and pharmacokinetics (DMPK) profile and a dose-dependent inhibition of LTB4 production.
For research use only. We do not sell to patients.
The (S)-BI 665915 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
- CAS No.: 1360550-05-5
- Formula: C24H26N8O2
- Molecular Weight:458.52
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
IC50: 1.7 nM (FLAP) and 45 nM (FLAP functional in human whole blood)[1]
In Vitro
(S)-BI 665915 shows significantly weaker activity in mouse whole blood (mWB) assay than in human whole blood (mWB IC50=4800 nM; hWB IC50=45 nM)[1].
(S)-BI 665915 shows a modest human hepatocyte clearance (41% percent of hepatic blood flow) and relatively high plasma protein binding (unbound fraction of 4.7%)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
(S)-BI 665915 (iv of 1 mg/kg or po of 10 mg/kg) shows low iv plasma clearance in all three species, with clearance values of 7 % Qh in rat, 2.8 % Qh in dog, and 3.6 % Qh in cynomolgus monkey, respectively. The volume of distribution (Vss) across species tested is in a range of 0.5 to 1.2 L/kg, and the bioavailability was good (45 to 63 %) in all species tested[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice[1]
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Dosage:1, 3, 10, 30, 100 mg/kg (Pharmacokinetic Analysis)
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Administration:Oral
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Result:Demonstrated dose-dependent LTB4 production inhibition in mouse whole blood, 2 h after single oral dose.
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Animal Model:Rat; dog; cynomolgus monkey[1]
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Dosage:1 mg/kg (iv) or 10 mg/kg (po)
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Administration:Iv or po
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Result:Showed low iv plasma clearance in all three species, with clearance values of 7 % Qh in rat, 2.8 % Qh in dog, and 3.6 % Qh in cynomolgus monkey, respectively.
Chemical Information
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CAS No. 1360550-05-5
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Molecular Weight 458.52
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Formula C24H26N8O2
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SMILES
O=C(N(C)C)CN1N=CC(C2=NC([C@@](C3CC3)(C4=CC=C(C5=CN=C(N)N=C5)C=C4)C)=NO2)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex
Purity & Documentation
References
[1]. Takahashi H, et al. Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915). J Med Chem. 2015 Feb 26;58(4):1669-90. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)