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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H17ClN6O
Molecular Weight 416.863
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DUVELISIB

SMILES

C[C@H](NC1=NC=NC2=C1N=CN2)C3=CC4=C(C(Cl)=CC=C4)C(=O)N3C5=CC=CC=C5

InChI

InChIKey=SJVQHLPISAIATJ-ZDUSSCGKSA-N
InChI=1S/C22H17ClN6O/c1-13(28-21-19-20(25-11-24-19)26-12-27-21)17-10-14-6-5-9-16(23)18(14)22(30)29(17)15-7-3-2-4-8-15/h2-13H,1H3,(H2,24,25,26,27,28)/t13-/m0/s1

HIDE SMILES / InChI

Description

Duvelisib (IPI-145), is an orally available, small-molecule, selective dual inhibitor of phosphatidylinositol 3 kinase (PI3K) δ and γ isoforms originated by Intellikine (owned by Takeda) and developed by Infinity Pharmaceuticals. Orally administered duvelisib was rapidly absorbed, with a dose-proportional increase in exposure. The compound produced a half-life of approximately 7-12 hours, following 14 days of dosing. Duvelisib exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation. Duvelisib blockade of PI3K-δ and PI3K-γ potentially lead to significant therapeutic effects in multiple inflammatory, autoimmune, and hematologic diseases. The molecule is in phase III development as a combination therapy for patients with haematological malignancies such as chronic lymphocytic leukemia and follicular lymphoma.

CNS Activity

Approval Year

PMID

PMID

TitleDatePMID
PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models.
2013 Nov 21
IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells.
2014 Dec 4
Novel phosphoinositide 3-kinase δ,γ inhibitor: potent anti-inflammatory effects and joint protection in models of rheumatoid arthritis.
2014 Feb
IPI-145 shows promise in CLL patients.
2014 Feb
PI3-kinase inhibitors in chronic lymphocytic leukemia.
2014 Mar
The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL.
2015 Sep
Targeting PI3Kδ and PI3Kγ signalling disrupts human AML survival and bone marrow stromal cell mediated protection.
2016 Jun 28
Patent

Sample Use Guides

In Vivo Use Guide
25-75 mg twice daily for five to 28 days
Route of Administration: Oral
In Vitro Use Guide
0.25 to 5 uM IPI-145 exhibited concentration- and time-dependent induction of cytotoxicity in primary chronic lymphocytic leukemia cells
Name Type Language
DUVELISIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
1(2H)-ISOQUINOLINONE, 8-CHLORO-2-PHENYL-3-((1S)-1-(9H-PURIN-6-YLAMINO)ETHYL)-
Systematic Name English
IPI-145
Code English
DUVELISIB [INN]
Common Name English
(S)-3-(1-(9H-PURIN-6-YLAMINO)ETHYL)-8-CHLORO-2-PHENYLISOQUINOLIN-1(2H)-ONE
Systematic Name English
INK-1197
Code English
DUVELISIB [WHO-DD]
Common Name English
DUVELISIB [USAN]
Common Name English
INK-1147
Code English
Code System Code Type Description
PUBCHEM
50905713
Created by admin on Tue Mar 06 11:41:13 UTC 2018 , Edited by admin on Tue Mar 06 11:41:13 UTC 2018
PRIMARY SWITZERF
ChEMBL
CHEMBL3039502
Created by admin on Tue Mar 06 11:41:13 UTC 2018 , Edited by admin on Tue Mar 06 11:41:13 UTC 2018
PRIMARY
INN
9856
Created by admin on Tue Mar 06 11:41:13 UTC 2018 , Edited by admin on Tue Mar 06 11:41:13 UTC 2018
PRIMARY
EPA CompTox
1201438-56-3
Created by admin on Tue Mar 06 11:41:13 UTC 2018 , Edited by admin on Tue Mar 06 11:41:13 UTC 2018
PRIMARY
CAS
1201438-56-3
Created by admin on Tue Mar 06 11:41:13 UTC 2018 , Edited by admin on Tue Mar 06 11:41:13 UTC 2018
PRIMARY
EVMPD
SUB180102
Created by admin on Tue Mar 06 11:41:13 UTC 2018 , Edited by admin on Tue Mar 06 11:41:13 UTC 2018
PRIMARY