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Synonyms: CDZ-173 | CDZ173 | Example 67 [WO2012004299] | Joenja®
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].
Ligand Activity Visualisation ChartsThese 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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| References |
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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. |
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2. Duggan S, Al-Salama ZT. (2023)
Leniolisib: First Approval. Drugs, 83 (10): 943-948. [PMID:37256490] |
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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] |
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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] |
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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] |
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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] |
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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] |
