Duvelisib ( English Duvelisib ; other names IPI-145, INK-1197) is a drug from the group of selective inhibitors of phosphoinositide-3-kinase . It is a research drug for the treatment of non-Hodgkin lymphomas and chronic lymphocytic leukemia .
| Duvelisib | |
|---|---|
 | |
| Chemical compound | |
| IUPAC | 8-Chloro-2-phenyl-3 - [(1S) -1- (9H-purin-6-ylamino) ethyl] -1 (2H) -isoquinolinone |
| Gross formula | C 22 H 17 ClN 6 O |
| Molar mass | 416.86 |
| Cas | |
| PubChem | |
| Drugbank | |
| Classification | |
| Farmakol. Group | Antineoplastic and immunomodulating agents |
| ATX | |
| Route of administration | |
| Orally | |
| Other names | |
| Duvelisib | |
Mechanism of Action
Duvelisib is a double inhibitor of the catalytic subunits p110γ and p110δ of the enzyme phosphoinositide-3-kinase . Competitively replacing ATP molecules in ATP-binding "pockets" of catalytic subunits, Duvelisib causes complete inactivation of the enzyme. Duvelisib's dissociation constant is 0.24 nano mol for p110γ and 0.023 nano mol for p110δ. [one]
Clinical Trials
The catalytic subunits p110γ and p110δ of phosphoinositide-3-kinases are expressed exclusively in leukocytes , where they are involved in various cellular processes, such as division, differentiation, migration and immunocompetence. Thus, inhibition of p110γ and p110δ subunits is a highly specific treatment for blood cancer and inflammatory diseases. Clinical trials in patients with chronic lymphocytic leukemia have shown a positive effect in 88% of cases. The average therapeutic effect time was 3.7 months. Biochemical analysis showed a significant decrease in the activity of the signaling cascade of phosphoinositide-3-kinase and death of neoplastic cells. At the same time, side effects were minor and included mainly diarrhea, skin rash, neutropenia, and elevated liver enzymes. [2] Thus, Duvelisib has established itself as a new, effective treatment for chronic leukemia.
Notes
- ↑ Balakrishnan K , Peluso M , Fu M , Rosin NY , Burger JA , Wierda WG , Keating MJ , Faia K , O'Brien S , Kutok JL , Gandhi V. 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 // Leukemia. - 2015. - April 28 ( t. 29 , No. 9 ). - S. 1811-1822 . - ISSN 0887-6924 . - DOI : 10.1038 / leu.2015.105 .
- ↑ DUETTS: Global evaluation of duvelisib, a dual inhibitor of PI3K-δ, γ Archived November 20, 2015 on the Wayback Machine