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

Duvelisib (1201438-56-3) is a potent and selective (IC50’s: PI3Kα = 1602nM, PI3Kβ = 85nM, PI3Kδ= 2.5nM, PI3Kγ = 27nM) dual PI3Kδ/γ inhibitor.1 It inhibits B and T cell proliferation, blocks neutrophil migration, and inhibits basophil activation. Duvelisib antagonizes B-cell receptor cross-linking activated pro-survival signals in primary chronic lymphocytic leukemia cells.2?Duvelisib also shows preclinical/clinical activity against other hematologic malignancies such as Non-Hodgkins lymphoma, T-cell lymphoma, and others.3,4?Useful clinical agent for the treatment of various blood cancers. Low-dose treatment of T-cell-inflamed tumor models of head and neck cancers with Duvelisib enhanced responses to PD-L1 blockade via suppression of myeloid-derived suppressor cells.5?Higher doses reversed the effect due to suppression of tumor-infiltrating T lymphocytes

Uses

IPI 145 is an 1,2-dihydroisoquinolin-1(2H)-one derivative and has been developed as a modulator of PI3 kinase.

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.