leniolisib   Click here for help

GtoPdb Ligand ID: 9424

Synonyms: CDZ-173 | CDZ173 | Example 67 [WO2012004299] | Joenja®
Approved drug PDB Ligand Immunopharmacology Ligand
leniolisib is an approved drug (FDA (2023))
Compound class: Synthetic organic
Comment: Leniolisib (CDZ173) is an orally bioavailable, potent phosphatidylinositol 3-kinase inhibitor (PI3K) inhibitor, with selectivity for the PI3Kδ isoform [3]. Novartis originally developed CDZ173 as a treatment for autoimmune diseases, but has rapidly repurposed it for its potential in patients with Activated PI3K Delta Syndrome (APDS, a.k.a. p110 delta activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency, or PASLI). APDS is an ultra-rare genetic immunodeficiency disease characterised by lymphoproliferation, recurrent infections from childhood, and an increased risk of EBV-associated lymphoma. APDS is known to be caused by autosomal dominant, gain-of-function mutations in the PIK3CD gene which encodes the PI3Kδ protein [4,7].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 83.48
Molecular weight 450.2
XLogP 2.47
No. Lipinski's rules broken 0
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Canonical SMILES CCC(=O)N1CCC(C1)Nc1ncnc2c1CN(CC2)c1cnc(c(c1)C(F)(F)F)OC
Isomeric SMILES CCC(=O)N1CC[C@@H](C1)Nc1ncnc2c1CN(CC2)c1cnc(c(c1)C(F)(F)F)OC
InChI InChI=1S/C21H25F3N6O2/c1-3-18(31)30-6-4-13(10-30)28-19-15-11-29(7-5-17(15)26-12-27-19)14-8-16(21(22,23)24)20(32-2)25-9-14/h8-9,12-13H,3-7,10-11H2,1-2H3,(H,26,27,28)/t13-/m0/s1
1. Cooke NG, Fernandes GDSP, Graveleau N, Hebach C, Hogenauer K, Hollingworth G, Smith AB, Soldermann N, Stowasser F, Strang R et al.. (2012)
Tetrahydro-pyrido-pyrimidine derivatives.
Patent number: WO2012004299. Assignee: Novartis Ag. Priority date: 06/07/2010. Publication date: 12/01/2012.
2. Duggan S, Al-Salama ZT. (2023)
Leniolisib: First Approval.
Drugs, 83 (10): 943-948. [PMID:37256490]
3. Hoegenauer K, Soldermann N, Zécri F, Strang RS, Graveleau N, Wolf RM, Cooke NG, Smith AB, Hollingworth GJ, Blanz J et al.. (2017)
Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors.
ACS Med Chem Lett, 8 (9): 975-980. [PMID:28947947]
4. Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M et al.. (2014)
Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency.
Nat Immunol, 15 (1): 88-97. [PMID:24165795]
5. Rao VK, Webster S, Šedivá A, Plebani A, Schuetz C, Shcherbina A, Conlon N, Coulter T, Dalm VA, Trizzino A et al.. (2023)
A randomized, placebo-controlled phase 3 trial of the PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome.
Blood, 141 (9): 971-983. [PMID:36399712]
6. Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M et al.. (2017)
Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib.
Blood, 130 (21): 2307-2316. [PMID:28972011]
7. Wentink M, Dalm V, Lankester AC, van Schouwenburg PA, Schölvinck L, Kalina T, Zachova R, Sediva A, Lambeck A, Pico-Knijnenburg I et al.. (2017)
Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections.
Clin Immunol, 176: 77-86. [PMID:28104464]