IPI-549
IPI-549 Basic information
- Product Name:
- IPI-549
- Synonyms:
-
- IPI-549
- (S)-2-amino-N-(1-(8-((1-methyl-1H-pyrazol-4-yl)ethynyl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
- IPI-549(IPI549)
- IPI-549, 98%, a potent and selective PI3Kγ Inhibitor
- CS-2414
- IPI-549; IPI 549; IPI549.
- Pyrazolo[1,5-a]pyrimidine-3-carboxamide, 2-amino-N-[(1S)-1-[1,2-dihydro-8-[2-(1-methyl-1H-pyrazol-4-yl)ethynyl]-1-oxo-2-phenyl-3-isoquinolinyl]ethyl]-
- IPI549 (Eganelisib)
- CAS:
- 1693758-51-8
- MF:
- C30H24N8O2
- MW:
- 528.56
- Product Categories:
-
- API
- APIs
- Mol File:
- 1693758-51-8.mol
IPI-549 Chemical Properties
- Density
- 1.37±0.1 g/cm3(Predicted)
- storage temp.
- -20°C
- solubility
- Soluble in DMSO (up to at least 25 mg/ml)
- form
- solid
- pka
- 10.81±0.46(Predicted)
- color
- Pale yellow
- Stability:
- Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
- InChIKey
- XUMALORDVCFWKV-IBGZPJMESA-N
- SMILES
- C12=C(C(N[C@H](C3=CC4=C(C(=O)N3C3=CC=CC=C3)C(C#CC3=CN(C)N=C3)=CC=C4)C)=O)C(N)=NN1C=CC=N2
- CAS DataBase Reference
- 1693758-51-8
IPI-549 Usage And Synthesis
Description
IPI-549 (1693758-51-8) is a potent and highly selective inhibitor of PI3K-γ in both biochemical (IC50?= 16 nM) and cellular (IC50?= 12.2 nM) assays.1?Macrophage PI3K-γ has been found to be a critical switch between immune stimulation and suppression.2?IPI-549 has been used to reshape tumor immune microenvironments and promote cytotoxic T-cell-mediated tumor regression. Resistance to immune checkpoint blockade in 4T1 and B16-GMCSF tumors was overcome when anti-PD-1 or anti-CTLA4 therapies were combined with PI3K-γ inhibition via IPI-549.3?IPI-549 mono-treatment also resulted in tumor growth inhibition in several cancer cell lines.3?IPI-549 has also been shown to modulate P-glycoprotein-mediated multidrug resistance.4
Uses
IPI-549 is a selective phosphoinositide-3-kinase (PI3Kγ) Inhibitor. PI3Kγ inhibitors can be used to develop potential treatment for inflammatory and autoimmune diseases.
in vivo
Eganelisib (IPI549) demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration. In vivo (mice, rats, dog, and monkeys), Eganelisib has excellent oral bioavailability, low clearance, and distributed into tissues with a mean volume of distribution of 1.2 L/kg. Overall, Eganelisib has a favorable pharmacokinetic profile to allow potent and selective inhibition of PI3K-γ in vivo. The t1/2 of IPI-549 for mouse, rat, dog and monkey is 3.2, 4.4, 6.7 and 4.3 h, respectively. Eganelisib significantly reduces neutrophil migration in a dose dependent manner in this model when administered orally at all of the tested doses[1].
IC 50
PI3Kγ: 16 nM (IC50); PI3Kα: 3.2 μM (IC50); PI3Kβ: 3.5 μM (IC50)
References
[1] CATHERINE A. EVANS*. Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate[J]. ACS Medicinal Chemistry Letters, 2016, 7 9: 862-867. DOI:10.1021/acsmedchemlett.6b00238
[2] MEGAN M. KANEDA. PI3Kγ is a molecular switch that controls immune suppression[J]. Nature, 2016, 539 7629: 437-442. DOI:10.1038/nature19834
[3] OLIVIER DE HENAU. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells[J]. Nature, 2016, 539 7629: 443-447. DOI:10.1038/nature20554
[4] ALBERT A. DE VERA . Immuno-oncology agent IPI-549 is a modulator of P-glycoprotein (P-gp, MDR1, ABCB1)-mediated multidrug resistance (MDR) in cancer: In vitro and in vivo[J]. Cancer letters, 2019, 442: Pages 91-103. DOI:10.1016/j.canlet.2018.10.020
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