| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 0.3 nM (FASN)[1]
Fatty acid synthase (FASN). IPI-9119 is a potent, selective, and irreversible inhibitor of FASN. FASN is a key enzyme in de novo lipogenesis, catalyzing the synthesis of palmitate from acetyl-CoA and malonyl-CoA. By inhibiting FASN, IPI-9119 disrupts fatty acid synthesis, which is essential for cancer cell proliferation and survival. |
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| 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].
IPI-9119 inhibits FASN with an IC50 of 0.3 nM in in vitro biochemical assays. It inhibits FASN in cellular occupancy assays with an IC50 of approximately 10 nM. At concentrations of 0.05, 0.1, 0.25, 0.5, and 5 µM for 6 days, IPI-9119 inhibits AR-FL and AR-V7 protein expression. At 0.1 and 0.5 µM for 6 days, it inhibits cell growth and induces cell death. |
| 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].
In vivo, IPI-9119 inhibits tumor growth in castration-resistant prostate cancer (CRPC) xenograft mouse models. The compound is orally active, making it suitable for convenient administration. By inhibiting FASN and disrupting lipid metabolism, IPI-9119 reduces tumor cell proliferation and survival. |
| Enzyme Assay |
In vitro enzyme activity assays for IPI-9119 involve measuring its ability to inhibit FASN thioesterase domain activity. Recombinant FASN enzyme is incubated with its substrate in the presence of increasing concentrations of the compound. Enzyme activity is measured by detecting the release of coenzyme A or by using radiolabeled substrates, and the IC50 is determined (0.3 nM).
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| 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. In vitro cellular assays for IPI-9119 involve treating cancer cell lines (such as prostate cancer cells) with the compound and measuring its effects on cell growth, fatty acid synthesis, and signaling pathways. Readouts include inhibition of cell proliferation, induction of cell death, and inhibition of AR-FL and AR-V7 protein expression. |
| 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. In vivo efficacy of IPI-9119 is evaluated in castration-resistant prostate cancer (CRPC) xenograft mouse models. The compound is administered orally. Efficacy endpoints include tumor growth inhibition, tumor regression, and survival. The compound's effects on FASN activity and lipid metabolism in tumor tissue can also be assessed. |
| ADME/Pharmacokinetics |
IPI-9119 has a molecular weight of 495.43 g/mol and a molecular formula of C24H19F2N5O5. It is orally active and soluble in DMSO (99 mg/mL). The compound has a purity of 99.65%. It shows more than 400-fold selectivity against several additional serine hydrolases.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for IPI-9119 in the provided literature. As a research compound, its safety profile would be an important consideration for in vivo applications. Potential toxicities could be related to its effects on fatty acid synthesis in normal tissues. Standard preclinical safety studies would be required.
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| References |
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| Additional Infomation |
IPI-9119 is an orally active, potent, selective, and irreversible FASN inhibitor with an IC50 of 0.3 nM. It inhibits FASN thioesterase domain by promoting acylation of the catalytic serine. IPI-9119 inhibits tumor growth in castration-resistant prostate cancer xenograft models. It has a molecular formula of C24H19F2N5O5 and a molecular weight of 495.43. It is a research tool and is not approved for clinical use.
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| Molecular Formula |
C24H19F2N5O5
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|---|---|
| Molecular Weight |
495.434972047806
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| Exact Mass |
495.135
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| CAS # |
1346564-56-4
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| PubChem CID |
68208572
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| Appearance |
White to off-white solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
845
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| Defined Atom Stereocenter Count |
0
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| 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
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| InChi Key |
VYXOFKWKPKVNID-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
4-[[4-(2,6-difluorophenyl)-5-oxotetrazole-1-carbonyl]-propan-2-ylamino]-3-phenoxybenzoic acid
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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: 100 mg/mL (201.84 mM)
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| 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. View More
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. |
| 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.
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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