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
References
1. Ali AY, Wu X, Eissa N, Hou S, Ghia JE, Murooka TT, Banerji V, Johnston JB, Lin F, Gibson SB et al.. (2018)
Distinct roles for phosphoinositide 3-kinases γ and δ in malignant B cell migration.
Leukemia, 32 (9): 1958-1969. [PMID:29479062]
2. Balakrishnan K, Peluso M, Fu M, Rosin NY, Burger JA, Wierda WG, Keating MJ, Faia K, O'Brien S, Kutok JL et al.. (2015)
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, 29 (9): 1811-22. [PMID:25917267]
3. Faia K, White K, Murphy E, Proctor J, Pink M, Kosmider N, McGovern K, Kutok J. (2018)
The phosphoinositide-3 kinase (PI3K)-δ,γ inhibitor, duvelisib shows preclinical synergy with multiple targeted therapies in hematologic malignancies.
PLoS ONE, 13 (8): e0200725. [PMID:30067771]
4. FDA. 
FDA Approves Copiktra.
Accessed on 25/09/2018. Modified on 25/09/2018. drugs.com, https://www.drugs.com/newdrugs/fda-approves-copiktra-duvelisib-capsules-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-4822.html?utm_source=ddc&utm_medium=email&utm_campaign=FDA+Approves+Copiktra+%28duvelisib%29+Capsules+for+Chronic+Lymphocytic+Leukemia%2FSmall+Lymphocytic+Lymphoma+and+Follicular+Lymphoma
5. FDA. 
duvelisib (COPIKTRA, Verastem, Inc.) for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Accessed on 25/09/2018. Modified on 25/09/2018. www.fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm621503.htm?utm_campaign=Oncology%209%2F24%2F2018%20&utm_medium=email&utm_source=Eloqua&elqTrackId=af90d9a841eb4460a1049510b7a4b8e1&elq=929604b9a11d4b8cbf1547ff884e7a8c&elqaid=5216&elqat=1&elqCampaignId=4172
6. Flinn IW, O'Brien S, Kahl B, Patel M, Oki Y, Foss FF, Porcu P, Jones J, Burger JA, Jain N et al.. (2018)
Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies.
Blood, 131 (8): 877-887. [PMID:29191916]
7. Flinn IW, Patel M, Oki Y, Horwitz S, Foss FF, Allen K, Douglas M, Stern H, Sweeney J, Kharidia J et al.. (2018)
Duvelisib, an oral dual PI3K-δ, γ inhibitor, shows clinical activity in indolent non-Hodgkin lymphoma in a phase 1 study.
Am J Hematol, 93 (11): 1311-1317. [PMID:30033575]
8. Lampson BL, Brown JR. (2017)
PI3Kδ-selective and PI3Kα/δ-combinatorial inhibitors in clinical development for B-cell non-Hodgkin lymphoma.
Expert Opin Investig Drugs, 26 (11): 1267-1279. [PMID:28945111]
9. O'Brien S, Patel M, Kahl BS, Horwitz SM, Foss FM, Porcu P, Jones J, Burger J, Jain N, Allen K et al.. (2018)
Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study.
Am J Hematol, 93 (11): 1318-1326. [PMID:30094870]
10. Ren P, Yi Liu, Wilson TE, Li L, Chan K, Rommel C. (2012)
Substituted isoquinolin-1(2H)-ones, and methods of use thereof.
Patent number: US8193182. Assignee: Intellikine, Inc.. Priority date: 04/01/2008. Publication date: 05/06/2012.
11. Robak P, Robak T. (2017)
Novel synthetic drugs currently in clinical development for chronic lymphocytic leukemia.
Expert Opin Investig Drugs, 26 (11): 1249-1265. [PMID:28942659]
12. Vangapandu HV, Jain N, Gandhi V. (2017)
Duvelisib: a phosphoinositide-3 kinase δ/γ inhibitor for chronic lymphocytic leukemia.
Expert Opin Investig Drugs, 26 (5): 625-632. [PMID:28388280]
13. Willemsen-Seegers N, Uitdehaag JCM, Prinsen MBW, de Vetter JRF, de Man J, Sawa M, Kawase Y, Buijsman RC, Zaman GJR. (2017)
Compound Selectivity and Target Residence Time of Kinase Inhibitors Studied with Surface Plasmon Resonance.
J Mol Biol, 429 (4): 574-586. [PMID:28043854]
14. Winkler DG, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM et al.. (2013)
PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models.
Chem Biol, 20 (11): 1364-74. [PMID:24211136]