U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C30H24N8O2
Molecular Weight 528.5651
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EGANELISIB

SMILES

C[C@@]([H])(c1cc2cccc(C#Cc3cnn(C)c3)c2c(=O)n1-c4ccccc4)N=C(c5c(N)nn6cccnc56)O

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

HIDE SMILES / InChI

Molecular Formula C30H24N8O2
Molecular Weight 528.5651
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27828943 | https://clinicaltrials.gov/ct2/show/NCT02637531 | https://www.google.com/patents/WO2015051244A1

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
16.0 nM [IC50]
3200.0 nM [IC50]
3500.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells.
2016 Nov 17
Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate.
2016 Sep 8
Patents

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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:53:44 UTC 2021
Edited
by admin
on Fri Jun 25 23:53:44 UTC 2021
Record UNII
FOF5155FMZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
EGANELISIB
USAN   INN  
Official Name English
2-amino-N-[(1S)-1-{8-[2-(1-methyl-1H-pyrazol-4-yl)ethynyl]-1-oxo-2-phenyl- 1,2-dihydroisoquinolin-3-yl}ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
Systematic Name English
EGANELISIB [INN]
Common Name English
PI3K-GAMMA INHIBITOR IPI-549
Common Name English
IPI-549
Code English
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)-
Systematic Name English
(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
Systematic Name English
EGANELISIB [WHO-DD]
Common Name English
EGANELISIB [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Fri Jun 25 23:53:44 UTC 2021 , Edited by admin on Fri Jun 25 23:53:44 UTC 2021
NCI_THESAURUS C2152
Created by admin on Fri Jun 25 23:53:44 UTC 2021 , Edited by admin on Fri Jun 25 23:53:44 UTC 2021
Code System Code Type Description
PUBCHEM
91933883
Created by admin on Fri Jun 25 23:53:44 UTC 2021 , Edited by admin on Fri Jun 25 23:53:44 UTC 2021
PRIMARY
INN
11571
Created by admin on Fri Jun 25 23:53:44 UTC 2021 , Edited by admin on Fri Jun 25 23:53:44 UTC 2021
PRIMARY
FDA UNII
FOF5155FMZ
Created by admin on Fri Jun 25 23:53:44 UTC 2021 , Edited by admin on Fri Jun 25 23:53:44 UTC 2021
PRIMARY
NCI_THESAURUS
C125471
Created by admin on Fri Jun 25 23:53:44 UTC 2021 , Edited by admin on Fri Jun 25 23:53:44 UTC 2021
PRIMARY
CAS
1693758-51-8
Created by admin on Fri Jun 25 23:53:44 UTC 2021 , Edited by admin on Fri Jun 25 23:53:44 UTC 2021
PRIMARY
Related Record Type Details
ACTIVE MOIETY