leniolisib   

GtoPdb Ligand ID: 9424

Synonyms: CDZ-173 | CDZ173 | Example 67 [WO2012004299]
Compound class: Synthetic organic
Comment: Leniolisib is an orally active, potent phosphatidylinositol 3-kinase inhibitor (PI3K) inhibitor, with selectivity for the PI3Kδ isoform [2]. 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 a 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 [3,5].
2D Structure
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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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
InChI Key MWKYMZXCGYXLPL-ZDUSSCGKSA-N
Classification
Compound class Synthetic organic
IUPAC Name
1-[(3S)-3-[[6-[6-methoxy-5-(trifluoromethyl)pyridin-3-yl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]amino]pyrrolidin-1-yl]propan-1-one
International Nonproprietary Names
INN number INN
10255 leniolisib
Synonyms
CDZ-173 | CDZ173 | Example 67 [WO2012004299]
Comments
Leniolisib is an orally active, potent phosphatidylinositol 3-kinase inhibitor (PI3K) inhibitor, with selectivity for the PI3Kδ isoform [2]. 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 a 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 [3,5].
Database Links
CAS Registry No. 1354690-24-6 (source: WHO INN record)
ChEMBL Ligand CHEMBL3643413
GtoPdb PubChem SID 328083524
PubChem CID 57495353
RCSB PDB Ligand 9NQ
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