IPI-9119 is an orally bioactive, selective and irreversible FASN inhibitor (antagonist) with IC50 of 0.3 nM. IPI-9119 inhibits tumor growth in a castration-resistant prostate cancer (CRPC) xenograft mouse model.

Physicochemical Properties

Molecular Formula	C24H19F2N5O5
Molecular Weight	495.434972047806
Exact Mass	495.135
CAS #	1346564-56-4
PubChem CID	68208572
Appearance	White to off-white solid powder
LogP	5.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	6
Heavy Atom Count	36
Complexity	845
Defined Atom Stereocenter Count	0
SMILES	FC1C=CC=C(C=1N1C(N(C(N(C2=CC=C(C(=O)O)C=C2OC2C=CC=CC=2)C(C)C)=O)N=N1)=O)F
InChi Key	VYXOFKWKPKVNID-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H19F2N5O5/c1-14(2)29(19-12-11-15(22(32)33)13-20(19)36-16-7-4-3-5-8-16)23(34)31-24(35)30(27-28-31)21-17(25)9-6-10-18(21)26/h3-14H,1-2H3,(H,32,33)
Chemical Name	4-[[4-(2,6-difluorophenyl)-5-oxotetrazole-1-carbonyl]-propan-2-ylamino]-3-phenoxybenzoic acid
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

Targets	IC50: 0.3 nM (FASN)[1]
ln Vitro	In cellular occupancy experiments, IPI-9119 inhibits FASN with an IC50 of about 10 nM. It also exhibits selectivity against various other serine hydrolases that is greater than 400-fold[2]. IPI-9119 (0.1-0.5 μM; 6 days) causes cell cycle arrest and apoptosis in addition to inhibiting cell growth[1]. IPI-9119 (0.05-5 μM; 6 days) suppresses the expression of the AR-FL and AR-V7 proteins[1].
ln Vivo	In animal models with CRPC xenografts, IPI-9119 (SC pump infusion; 0.5 μL/h; 100 mg/mL; for 28 days) suppresses the formation of tumors[1].
Cell Assay	Cell Viability Assay[1] Cell Types: Prostate cancer (PCa) cells ( AD LNCaP, AI C4-2, LNCaP-95 and 22Rv1 AI cells) Tested Concentrations: 0.1, 0.5 μM Incubation Duration: 6 days Experimental Results: Inhibited PCa cell growth. Had no growth inhibition in FASN KO PCa cells. Cell Cycle Analysis[1] Cell Types: PCa cells Tested Concentrations: 0.1, 0.5 μM Incubation Duration: 6 days Experimental Results: diminished the proportion of S-phase cells and increased that of G0/G1-, sub-G1–phase cells and diminished expression of cyclin A2. Western Blot Analysis[1] Cell Types: PCa cells Tested Concentrations: 0.05, 0.1, 0.25, 0.5, 5 μM Incubation Duration: 6 days Experimental Results: Dramatically diminished AR-FL protein levels in AD LNCaP, AI C4-2 cells (expressing only AR-FL ) and diminished the expression of AR-V7 in LNCaP-95, 22Rv1 AI cells driven by this variant.
Animal Protocol	Animal/Disease Models: 8-10-week male Ncr Nu Castrated mice or castrated NOD male SCID with 22Rv1 or LNCaP-95 cells[1] Doses: 100 mg/mL Route of Administration: SC pump infusion (0.5 μL/h; 100 mg/mL); for 28 days Experimental Results: Inhibited tumor growth of castration-resistant prostate cancer ( CRPC) xenografts mouse models.
References	[1]. Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer. Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):631-640. [2]. Abstract 1891: Pharmacological target validation studies of fatty acid synthase in carcinoma using the potent, selective and orally bioavailable inhibitor IPI-9119.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (201.84 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.20 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 (4.20 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.20 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	2.0184 mL	10.0920 mL	20.1841 mL
	5 mM	0.4037 mL	2.0184 mL	4.0368 mL
	10 mM	0.2018 mL	1.0092 mL	2.0184 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.