BMS-986339 is an orally bioactive FXR agonist. BMS-986339 can form hydrogen bonds with His298 and ASN287 residues. BMS-986339 is indicated for primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), non-alcoholic steatohepatitis (NASH), and anti-fibrosis research.

Physicochemical Properties

Molecular Formula	C35H41F4N3O4
Molecular Weight	643.711363554001
Exact Mass	643.303
CAS #	2477873-64-4
PubChem CID	154683007
Appearance	Typically exists as solid at room temperature
LogP	6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	8
Heavy Atom Count	46
Complexity	1090
Defined Atom Stereocenter Count	0
InChi Key	AEMZJBZKICOPPC-UHFFFAOYSA-N
InChi Code	InChI=1S/C35H41F4N3O4/c1-30(2,36)29-40-28(41-46-29)33-15-12-32(13-16-33,14-17-33)21-42(27(43)24-19-34(45,20-24)35(37,38)39)26-7-5-6-23(18-26)22-8-10-25(11-9-22)31(3,4)44/h5-11,18,24,44-45H,12-17,19-21H2,1-4H3
Chemical Name	N-[[4-[5-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-3-yl]-1-bicyclo[2.2.2]octanyl]methyl]-3-hydroxy-N-[3-[4-(2-hydroxypropan-2-yl)phenyl]phenyl]-3-(trifluoromethyl)cyclobutane-1-carboxamide
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	BMS-986339 (Compound 32) at 0.1 nM–10 μM for 24 hours inhibits the activation of genes that express FGF19 in hepatocytes and BSEP (bile salt export pump) in Huh-7 cells [1]. In patch clamp tests, BMS-986339 inhibits cytochrome P450 activity (IC50: 8 μM (CYP2C8), 13.5 μM (CYP2C9)) and hERG channels (IC50: 4.5 μM) [1]. BMS-986339 inhibits hUGT1A1 (IC50: 4.85 μM) and the transporters OATP1B3 and BSEP, with IC50 values of 1.44 and 1.5 μM, respectively [1].
ln Vivo	In a mouse model of bile duct ligation (BDL), BMS-986339 (Compound 32, orally, 10 mg/kg, once daily for 9 days) induces the production of Fgf15 and demonstrates anti-fibrotic efficacy [1]. In mice and rats, BMS-986339 (orally or intravenously, 5 mg/kg or 1 mg/kg) has a long elimination half-life and low clearance [1].
Animal Protocol	Animal/Disease Models: Mouse bile duct ligation (BDL) model [1] Doses: 0.3, 1, 3 and 10 mg/kg, one time/day for 9 days. Route of Administration: Oral administration Experimental Results: Induced Fgf15 and SHP (small heterodimer partner) gene expression to similar extent in the ileum. Reduces the proportion of hydroxyproline to total protein content and reduces collagen levels. Animal/Disease Models: Male C57BL6 mice, male SD (SD (Sprague-Dawley)) rats (pharmacokinetic/PK/PK determination) [1] Doses: 5 mg/kg or 1 mg/kg Route of Administration: po (po (oral gavage)) intravenous (iv) (iv)injection Experimental Results: BMS-986339 (compound 32) pharmacokinetic/PK/PK characteristics. Parameters Male C57BL6 Mouse Male SD (SD (Sprague-Dawley)) Rat Dose (mg/kg) iv 1 1 Dose (mg/kg) po 5 2 Vss (L/kg) iv 2.2 5.2 AUC Total (μM·h) iv 16.4 6.6 AUC Total (μM·h) ) PO 56.6 5.8 t1/2 h (iv) 16 18 Fp.o. 69 40
References	[1]. Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2022 Jul 14;65(13):8948-8960.

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	1.5535 mL	7.7675 mL	15.5349 mL
	5 mM	0.3107 mL	1.5535 mL	3.1070 mL
	10 mM	0.1553 mL	0.7767 mL	1.5535 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.