| Stereochemistry | ABSOLUTE |
| Molecular Formula | C30H24N8O2 |
| Molecular Weight | 528.564 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H](NC(=O)C1=C2N=CC=CN2N=C1N)C3=CC4=C(C(=O)N3C5=CC=CC=C5)C(=CC=C4)C#CC6=CN(C)N=C6
InChI
InChIKey=XUMALORDVCFWKV-IBGZPJMESA-N
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
| Molecular Formula | C30H24N8O2 |
| Molecular Weight | 528.564 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
IPI-549 is an orally bioavailable, highly selective small molecule inhibitor of the gamma isoform of phosphoinositide-3 kinase (PI3K-gamma) with potential immunomodulating and antineoplastic activities. Upon administration, IPI-549 prevents the activation of the PI3K-gamma-mediated signaling pathways, which may lead to a reduction in cellular proliferation in PI3K-gamma-expressing tumor cells. In addition, this agent is able to modulate anti-tumor immune responses and inhibit tumor-mediated immunosuppression. Unlike other isoforms of PI3K, the gamma isoform is overexpressed in certain tumor cell types and immune cells; its expression increases tumor cell proliferation and survival. By selectively targeting the gamma isoform, PI3K signaling in normal, non-neoplastic cells is minimally or not affected, which results in a reduced side effect profile. Preclinical data in multiple solid tumor models have demonstrated that IPI-549 targets immune cells and alters the immune-suppressive microenvironment, promoting an anti-tumor immune response that leads to tumor growth inhibition. A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing.
Originator
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
IPI-549 daily dose administered orally in 28-day cycles
Route of Administration:
Oral
SKOV-3 cells were seeded into 96-well cell culture-grade plates at a density of 200,000 cells/200 μL/well of RPMI-1640 (Life Technologies) with 10% FBS (Sigma). Cells were incubated overnight at 5% CO2 and 37 °C. Compound 26 (IPI-549) was added to the cells, resulting in a final DMSO concentration of 0.5%, and incubated for 30 minutes at 5% CO2 and 37 °C. Media was then aspirated and 50 μL/well of ice-cold lysis buffer was added. Plates were incubated on ice for 5 minutes and then centrifuged at 3000 rpm at 4 °C for 5 minutes.
