| Identification | Back Directory | [Name]
IPI 145 | [CAS]
1201438-56-3 | [Synonyms]
IPI-14
IPI 145
IPI-145
Duvelisib
IPI-145, >=98%
IPI-145 (INK-1197)
IPI 145 (Duvelisib)
Duvelisib
INK 1197
IPI-145, INK 1197, Duvelisib
Duvelisib (IPI-145, INK1197)
Duvelisib, 98%, a novel and selective PI3K δ/γ inhibitor
8-Chloro-2-phenyl-3-[(1S)-1-(9H-purin-6-ylamino)ethyl]-1(2H)-isoquinolinone
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) | [EINECS(EC#)]
200-256-5 | [Molecular Formula]
C22H16ClN6O | [MDL Number]
MFCD15144635 | [MOL File]
1201438-56-3.mol | [Molecular Weight]
415.855 |
| Chemical Properties | Back Directory | [Melting point ]
205-206o C | [Boiling point ]
757.8±60.0 °C(Predicted) | [density ]
1.474±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to at least 25 mg/ml) | [form ]
White solid. | [pka]
10.05±0.10(Predicted) | [color ]
White | [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. | [InChI]
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 | [InChIKey]
SJVQHLPISAIATJ-ZDUSSCGKSA-N | [SMILES]
C1(=O)C2=C(C=CC=C2Cl)C=C([C@@H](NC2=C3C(=NC=N2)NC=N3)C)N1C1=CC=CC=C1 |
| Hazard Information | Back Directory | [Uses]
IPI 145 is an 1,2-dihydroisoquinolin-1(2H)-one derivative and has been developed as a modulator of PI3 kinase. | [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 | [Definition]
ChEBI: 8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]-1-isoquinolinone is a member of isoquinolines. | [Brand name]
Copiktra | [General Description]
Class: lipid kinase;
Treatment: CLL, SLL, FL;
Other name: INK1197, IPI145;
Oral bioavailability = 42%;
Elimination half-life = 4.7 h;
Protein binding = 98% | [Pharmacokinetics]
The recommended dose of duvelisib is 25 mg
twice daily, much lower than that of idelalisib (150 mg,
bid). Duvelisib is rapidly absorbed, with a peak
concentration after 1–2 h. Following the
administration of 25 mg of duvelisib, the absolute
bioavailability in healthy volunteers is 42%. It is
eliminated with a short half-life of 4.7 h, thus
requiring twice daily administration. | [Synthesis]
IPI145 Intermediate-5 (Compound 10) (200 g) was taken as raw material and suspended in a solvent mixture of ethanol (900 mL; 4.5 v/v) and water (300 mL; 1.5 v/v) at 22 °C. Subsequently, concentrated hydrochloric acid (300 mL; 1.5 v/v) was slowly added and the reaction was stirred at 25-35 °C for 1.5 h until all solids were completely dissolved to form a dark brown solution. Upon completion of the reaction, ammonium hydroxide (260 mL) was added to adjust the pH to 8-9. Next, the product seed of polycrystalline type C (0.5 g) was added (type A seed could also be used) and the reaction system was maintained for 10 min, followed by the slow addition of water (3 L; 15 v/v) over a period of 2 h to induce crystallization. The reaction mixture was continued to be stirred at 20-25 °C for 3.5 h and then filtered. The filter cake was washed sequentially with water (1 L; 5 v/v) and heptane (800 mL; 4 v/v), and finally dried under vacuum at 52 °C for 23 h. The target product (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenyl-1(2H)-isoquinolone was obtained as 155.5 g, in 93.5% yield, with a purity of 99.6% (AUC), and an p enantiomeric excess value of 93.8% (chiral HPLC). | [target]
PI3K-δ | [IC 50]
 | [Metabolism]
Duvelisib is
primarily metabolized by CYP3A4 to give a monooxidation product, IPI-656, which has no
pharmacologically relevant activity.
 | [storage]
Store at -20°C | [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 |
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| Company Name: |
J & K SCIENTIFIC LTD.
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| Telephone: |
18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
| Company Name: |
NCE Biomedical Co.,Ltd.
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| Telephone: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15748/0_EN.htm |
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