1201438-56-3

Basic information

• Product Name: IPI 145
• Synonyms: IPI-145;IPI-145 (INK-1197);8-Chloro-2-phenyl-3-[(1S)-1-(9H-purin-6-ylamino)ethyl]-1(2H)-isoquinolinone;Duvelisib;Duvelisib (IPI-145, INK1197);1(2H)-Isoquinolinone, 8-chloro-2-phenyl-3-[(1S)-1-(9H-purin-6-ylamino)ethyl]-;8-Chloro-2-phenyl-3-[(1S)-1-(9H-purin-6-ylamino)ethyl]-1(2H)-isoquinolinone Duvelisib (IPI-145, INK1197);Duvelisib INK 1197
• CAS NO: 1201438-56-3
• Molecular Formula: C₂₂H₁₇ClN₆O
• Molecular Weight: 415.85504
• EINECS: 200-256-5
• Product Categories: reference inhibitors;Inhibitors
• Mol File: 1201438-56-3.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 757.8±60.0 °C(Predicted)
• Appearance: /
• Density: 1.474±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to at least 25 mg/ml)
• PKA: 10.05±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: IPI 145(CAS DataBase Reference)
• NIST Chemistry Reference: IPI 145(1201438-56-3)
• EPA Substance Registry System: IPI 145(1201438-56-3)

Safety Data

• Hazardous Substances Data: 1201438-56-3(Hazardous Substances Data)

Usage

Description

IPI 145, also known as Duvelisib, is a potent and selective dual PI3Kδ/γ inhibitor. It is a 1,2-dihydroisoquinolin-1(2H)-one derivative that has been developed as a modulator of PI3 kinase. IPI 145 exhibits inhibitory effects on B and T cell proliferation, blocks neutrophil migration, and inhibits basophil activation. It also antagonizes B-cell receptor cross-linking activated pro-survival signals in primary chronic lymphocytic leukemia cells.

Uses

Used in Hematologic Malignancies:
IPI 145 is used as an inhibitor for the treatment of various blood cancers, including chronic lymphocytic leukemia, Non-Hodgkin's lymphoma, and T-cell lymphoma. It modulates the PI3 kinase pathway, which is often dysregulated in these malignancies, leading to improved treatment outcomes.
Used in Immune Modulation:
IPI 145 is used as an immune modulator in T-cell-inflamed tumor models of head and neck cancers. Low-dose treatment enhances responses to PD-L1 blockade by suppressing myeloid-derived suppressor cells. However, higher doses may reverse the effect due to suppression of tumor-infiltrating T lymphocytes.
Used in Pharmaceutical Research:
IPI 145 is used as a research tool for studying the role of PI3 kinase in various cellular processes and diseases. Its potent and selective inhibition of PI3Kδ and PI3Kγ makes it a valuable compound for investigating the molecular mechanisms underlying PI3 kinase-mediated signaling pathways.

References

1) Winkler?et al.?(2013),?PI3K-δ and PI3K-γ Inhibition by IPI-145 Abrogates Immune Response and Suppresses Activity in Autoimmune and Inflammatory Disease Models;?Chem. Biol.?20?1309 2) Dong?et al.?(2014),?IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells;?Blood?124?3583 3) Flinn?et al.?(2018),?Duvelisib, a novel dual inhibitor of PI3K-δ/γ, is clinically active in advances hematologic malignancies;?Blood?131?877 4) Faia?et al.?(2018),?The phosphoinositide-3 kinase (PI3K)-δ,γ inhibitor, duvelisib, shows preclinical synergy with multiple targeted therapies in hematologic malignancies;?PLoS One?13?e0200725 5) Davis?et al.?(2017),?Anti-PD-L1 Efficacy Can Be Enhanced by Inhibition of Myeloid-Derived Suppressor Cells with a Selective Inhibitor of PI3Kδ/γ;?Cancer Res.?77?2607

Upstream product

• 1386861-47-7 tert-butyl (S)-(4-(3-chloro-2-(phenylcarbamoyl)phenyl)-3-oxobutane-2-yl)carbamate 
• 89894-44-0 2-chloro-6-methylbenzoyl chloride 
• 1350643-72-9 (S)-3-(1-aminoethyl)-8-chloro-2-phenylisoquinoline-1(2H)-one 
• 7306-68-5 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 
• 1386861-46-6 2-chloro-6-methyl-N-phenylbenzamide 
• 1350643-73-0 8-chloro-2-phenyl-3-((1S)-1-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one 
• 21327-86-6 2-chloro-6-methylbenzoic acid 
• 62-53-3 aniline 

Downstream Products

• 1350643-09-2 (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-2-phenyl-8-(pyrrolidin-1-yl)isoquinolin-1(2H)-one 
• 1350643-11-6 (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-2-phenyl-8-(1H-pyrazol-4-yl)isoquinolin-1(2H)-one 
• 1350643-63-8 (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-1-oxo-2-phenyl-1,2-dihydroisoquinoline-8-carbaldehyde 
• 1350643-17-2 (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-1-oxo-2-phenyl-1,2-dihydroisoquinoline-8-carbonitrile 
• 1350643-14-9 (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-ethyl-2-phenylisoquinolin-1(2H)-one 

Relevant articles and documents

PROCESSES FOR PREPARING ISOQUINOLINONES AND SOLID FORMS OF ISOQUINOLINONES

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.