duvelisib   Click here for help

GtoPdb Ligand ID: 7795

Synonyms: compound 4904 [Patent US8193182] [10] | Copiktra® | INK-1197 | IPI-145
Approved drug Immunopharmacology Ligand
duvelisib is an approved drug (FDA (2018), EMA (2021))
Compound class: Synthetic organic
Comment: Duvelisib is an orally active, dual inhibitor of phosphoinositide-3 kinase (PI3K)-δ and PI3K-γ [14]. It was developed for the treatment of advanced hematolgical malignancies including CLL, SLL and FL [8,11-12].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 87.97
Molecular weight 416.12
XLogP 5.17
No. Lipinski's rules broken 1
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Canonical SMILES Clc1cccc2c1c(=O)n(c(c2)C(Nc1ncnc2c1[nH]cn2)C)c1ccccc1
Isomeric SMILES Clc1cccc2c1c(=O)n(c(c2)[C@@H](Nc1ncnc2c1[nH]cn2)C)c1ccccc1
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
Bioactivity Comments
Duvelisib binds 1000-fold more potently to PI3Kδ isoform in comparison to the α isoform and 19 times more potently than to the γ isoform. Duvelisib has a comparable KD and association rate for the PI3Kδ isoform to idelalisib, but has a much slower dissociation rate, resulting in a long target residency time (τ) of 2 hours [13].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta Primary target of this compound Hs Inhibitor Inhibition 8.6 pIC50 - 14
pIC50 8.6 (IC50 2.5x10-9 M) [14]
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma Primary target of this compound Hs Inhibitor Inhibition 7.6 pIC50 - 14
pIC50 7.6 (IC50 2.7x10-8 M) [14]
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta Hs Inhibitor Inhibition 7.1 pIC50 - 14
pIC50 7.1 (IC50 8.5x10-8 M) [14]
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha Hs Inhibitor Inhibition 5.8 pIC50 - 14
pIC50 5.8 (IC50 1.602x10-6 M) [14]