(S)-BI 665915 is an orally bioactive, oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitor (antagonist) with IC50 of 1.7 nM for binding to FLAP. (S)-BI 665915 inhibits FLAP function in human whole blood with IC50 of 45 nM. (S)-BI 665915 displays excellent metabolic and pharmacokinetic (DMPK) profiles of active molecules across species and dose-dependent inhibition of LTB4 production.

Physicochemical Properties

Molecular Formula	C24H26N8O2
Molecular Weight	458.52
Exact Mass	458.217
CAS #	1360550-05-5
PubChem CID	68050136
Appearance	Typically exists as solid at room temperature
LogP	2.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	34
Complexity	705
Defined Atom Stereocenter Count	1
SMILES	C[C@](C1CC1)(C2=CC=C(C=C2)C3=CN=C(N=C3)N)C4=NOC(=N4)C5=CN(N=C5)CC(=O)N(C)C
InChi Key	QGPXEIMWTKWHMH-XMMPIXPASA-N
InChi Code	InChI=1S/C24H26N8O2/c1-24(19-8-9-19,18-6-4-15(5-7-18)16-10-26-23(25)27-11-16)22-29-21(34-30-22)17-12-28-32(13-17)14-20(33)31(2)3/h4-7,10-13,19H,8-9,14H2,1-3H3,(H2,25,26,27)/t24-/m1/s1
Chemical Name	2-[4-[3-[(1S)-1-[4-(2-aminopyrimidin-5-yl)phenyl]-1-cyclopropylethyl]-1,2,4-oxadiazol-5-yl]pyrazol-1-yl]-N,N-dimethylacetamide
Synonyms	(S)BI 665915; (S) BI-665915
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	In the mouse whole blood (mWB) experiment, (S)-BI 665915 exhibited noticeably less activity than the human whole blood (mWB IC50=4800 nM; hWB IC50=45 nM) [1]. (S)-BI 665915 has a reasonably strong plasma protein binding (unbound fraction 4.7%), along with modest human hepatocyte clearance (41% of hepatic blood flow) [1].
ln Vivo	(S)-BI 665915 (oral; 1-100 mg/kg) shown that two hours after a single oral dose, mouse whole blood showed a dose-dependent suppression of LTB4 synthesis [1]. With clearance values of 7% Qh in rats and 7% Qh in dogs, (S)-BI 665915 (1 mg/kg IV or 10 mg/kg PO) demonstrated limited venous plasma clearance in all three species. for cynomolgus monkeys, 2.8% Qh and 3.6% Qh, respectively. Each of the studied species had a good volume of distribution (Vss) ranging from 0.5 to 1.2 L/kg and a good bioavailability (45–63%) [1].
Animal Protocol	Animal/Disease Models: C57BL/6 mice[1] Doses: 1, 3, 10, 30, 100 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Oral Experimental Results:2 hrs (hrs (hours)) after a single oral administration, mouse whole blood Dose-dependent LTB4 production was shown to inhibit dose. Animal/Disease Models: Rat; Dog; Cynomolgus Monkey [1] Doses: 1 mg/kg (IV) or 10 mg/kg (OR) Route of Administration: IV or PO Experimental Results: IV plasma of all three species The clearance rates were all low, with the clearance rate in rats being 7% Qh, the Qh in dogs being 2.8%, and the Qh in cynomolgus monkeys being 3.6%.
References	[1]. 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.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1809 mL	10.9046 mL	21.8093 mL
	5 mM	0.4362 mL	2.1809 mL	4.3619 mL
	10 mM	0.2181 mL	1.0905 mL	2.1809 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.