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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key SJVQHLPISAIATJ-ZDUSSCGKSA-N
No information available.
Summary of Clinical Use Click here for help
Early stage clinical efficacy was reported in hematological malignancies [3,6-7,9]. Duvelisib (under its long chemical name (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one) was initially granted orphan drug (OD) designation by the EMA for the treatment of chronic lymphocytic leukemia (CLL) and by the FDA for CLL and follicular lymphoma. Full FDA approval was granted in September 2018 for the treatment of relapsed/refractory CLL/SLL after at least two prior therapies [5]. Accelerated approval for the treatment relapsed/refractory follicular lymphoma (FL) after at least two prior systemic therapies was also granted at this time. Duvelisib packaging carries a boxed warning to alert prescribers and patients to the risk of 4 fatal and/or serious toxicities that are associated with use of ths drug. These 4 adverse reactions are infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.
Click here to link to ClinicalTrials.gov's full list of duvelisib studies.
In October 2019 FDA OD designation was granted for the treatment of T-cell lymphoma. The EMA has approved duvelisib (May 2021) as a treatment for CLL and follicular lymphoma
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Phosphoinositide-3 kinase (PI3K)-δ and PI3K-γ are preferentially expressed in immune cells. Inhibitors targeting these isozymes are hypothesized to modulate both the adaptive and innate immune responses, generating an anti-inflammatory effect. As the PI3Ks are essential mediators of the chemokine receptor signalling that is required for migration and survival of malignant hematological cells [1], inhibitors have been exploited as treatments for hematological cancers. Duvelisib has been shown to promote apoptosis in malignant B cells [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04372602 Duvelisib to Combat COVID-19 Phase 2 Interventional Washington University School of Medicine