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Purity: ≥98%
Eganelisib (IPI 549; IPI549; IPI-549) is a novel, potent and selective small molecule PI3Kγ (phosphoinositide-3-kinase) inhibitor with potential anticancer and immunomodulatory activity. With an IC50 of 16 nM and >100-fold selectivity over other lipid and protein kinases, it inhibits PI3Kγ . IPI-549 is currently undergoing Phase 1 clinical testing in patients with advanced solid tumors. It exhibits positive pharmacokinetic properties and robust inhibition of PI3Kγ -mediated neutrophil migration in vivo.
| Targets |
PI3Kγ (IC50 = 16 nM); PI3Kα (IC50 = 3.2 μM); PI3Kβ (IC50 = 3.5 μM)
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| ln Vitro |
Eganelisib (IPI549) inhibits PI3Kγ with IC50 of 16 nM, with >100-fold selectivity over other lipid and protein kinases (PI3Kα IC50=3.2 μM, PI3Kβ IC50=3.5 μM, PI3Kδ IC50>8.4 μM). Eganelisib is evaluated for activity across all Class I PI3K isoforms. The activity of eganelisib is assessed across all Class I PI3K isoforms. The individual rates constants and for PI3K-α, β and δ are measured using equilibrium fluorescent titration to ascertain the binding affinity of Eganelisib for PI3K-γ. Eganelisib is a remarkably tight binder to PI3Kγ with a Kd of 290 pM and >58-fold weaker affinity for other Class I PI3K isoforms (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). Eganelisib exhibits excellent PI3K-γ potency (IC50=1.2 nM) and selectivity against other Class I PI3K isoforms (>146-fold) in PI3K-α, -β, -γ, and -δ dependent cellular phospho-AKT assays. Cellular IC50s for Class I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) are determined in SKOV-3, 786-O, RAW 264.7, and RAJI cells, respectively, by monitoring inhibition of pAKT S473 by ELISA. Furthermore, Eganelisib dose dependently inhibits PI3Kγ dependent bone marrow-derived macrophage (BMDM) migration. Eganelisib is selective against a panel of 80 GPCRs, ion channels, and transporters at 10 μM[1]
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| ln Vivo |
Eganelisib (IPI549) exhibits advantageous pharmacokinetic characteristics and potent PI3K-mediated neutrophil migration inhibition. Eganelisib has excellent oral bioavailability, low clearance, and is distributed into tissues with a mean volume of distribution of 1.2 L/kg in vivo (in mice, rats, dogs, and monkeys). Overall, Eganelisib has a good pharmacokinetic profile that enables potent and precise PI3K- in vivo inhibition. The t1/2 of IPI-549 is 3.2, 4.4, 6.7, and 4.3 hours for mice, rats, dogs, and monkeys, respectively. In this model, oral administration of eganelisib at all of the tested doses significantly reduces neutrophil migration in a dose-dependent manner[1].
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| Cell Assay |
At a density of 200,000 cells/200 L/well of RPMI-1640 with 10% FBS, SKOV-3 cells are seeded into 96-well cell culture-grade plates. Cells are incubated for the entire night at 5% CO2 and 37 °C. The cells are treated with substances, resulting in a final concentration of 0.5% DMSO, and then incubated for 30 minutes at 37 °C and 5% CO2. Following the aspiration of the media, 50 L of ice-cold lysis buffer is added to each well. After five minutes of incubation on ice, plates are centrifuged at 3000 rpm for five minutes at 4 °C.
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| Animal Protocol |
The mice used in this study are C57BL/6J and Balb/c mice, aged 6 to 8 weeks. In the first day of the experiment, tumor cells are injected intradermally (i.d.) in the right flank. Once per day, 15 mg/kg of eganelisib is given orally through gavage. Beginning on day seven after tumor implantation and lasting until day twenty-one. Transportation (5% NMP, 95% PEG) is given to the control groups. Every second or third day, tumors are calibrated with a ruler to measure their volume (length, width, and height). when the total tumor volume reaches 2500 mm3, or when there are signs of distress in the animal. Tumors are then isolated and preserved in ice until needed[2].
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| References |
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| Molecular Formula |
C30H24N8O2
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| Molecular Weight |
528.58
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| Exact Mass |
528.2022
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| Elemental Analysis |
C, 68.17; H, 4.58; N, 21.20; O, 6.05
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| CAS # |
1693758-51-8
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| Related CAS # |
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| Appearance |
Yellow solid powder
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| SMILES |
O=C1N(C2=CC=CC=C2)C([C@@H](NC(C3=C(N=CC=C4)N4N=C3N)=O)C)=CC5=CC=CC(C#CC6=CN(C)N=C6)=C51
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| InChi Key |
XUMALORDVCFWKV-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C30H24N8O2/c1-19(34-29(39)26-27(31)35-37-15-7-14-32-28(26)37)24-16-22-9-6-8-21(13-12-20-17-33-36(2)18-20)25(22)30(40)38(24)23-10-4-3-5-11-23/h3-11,14-19H,1-2H3,(H2,31,35)(H,34,39)/t19-/m0/s1
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.73 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 25.0 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: ≥ 2.5 mg/mL (4.73 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 25.0 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 | 1.8919 mL | 9.4593 mL | 18.9186 mL | |
| 5 mM | 0.3784 mL | 1.8919 mL | 3.7837 mL | |
| 10 mM | 0.1892 mL | 0.9459 mL | 1.8919 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.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02637531 | Active Recruiting |
Drug: IPI-549 (eganelisib) Drug: Nivolumab |
Melanoma (Part E) Mesothelioma (Part G) |
Infinity Pharmaceuticals, Inc. | December 2015 | Phase 1 |
| NCT03961698 | Active Recruiting |
Drug: IPI-549 (eganelisib) Drug: Atezolizumab |
Breast Cancer Renal Cell Carcinoma |
Infinity Pharmaceuticals, Inc. | December 17, 2019 | Phase 2 |
| NCT03980041 | Completed | Drug: IPI-549 (eganelisib) Drug: Nivolumab |
Bladder Cancer Urothelial Carcinoma |
Infinity Pharmaceuticals, Inc. | September 25, 2019 | Phase 2 |
Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-γ (26or IPI-549) with >100-fold selectivity over other lipid and protein kinases.ACS Med Chem Lett.2016 Jul 22;7(9):862-7. |
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Effect of compound26on migration of bone marrow derived macrophages (BMDM) in vitro.ACS Med Chem Lett.2016 Jul 22;7(9):862-7. |
(a) Effect of compound26on neutrophil migration in the mouse air pouch model.ACS Med Chem Lett.2016 Jul 22;7(9):862-7. |
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