GtoPdb Ligand ID: 9928

Synonyms: XC-302 | XC302
Compound class: Synthetic organic
Comment: Puquitinib is an orally active, PI3 kinase inhibitor that induces autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. Puquitinib is selective for p110δ relative to other PI3K class I enzymes. It is a clinical lead developed for antitumour activity [3].
Puquitinib is a 'pseudo' INN, that takes the form of an INN, but has not been submitted to the World Health Organisation for ratification.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 4
Topological polar surface area 91.41
Molecular weight 317.14
XLogP 2.71
No. Lipinski's rules broken 0
Canonical SMILES c1cnc2c(c1)cc(cc2)Nc1nc(NC2CC2)c2c(n1)nc[nH]2
Isomeric SMILES c1cnc2c(c1)cc(cc2)Nc1nc(NC2CC2)c2c(n1)nc[nH]2
InChI InChI=1S/C17H15N7/c1-2-10-8-12(5-6-13(10)18-7-1)22-17-23-15-14(19-9-20-15)16(24-17)21-11-3-4-11/h1-2,5-9,11H,3-4H2,(H3,19,20,21,22,23,24)
No information available.
Summary of Clinical Use
Puquitinib was found to be safe, with a promising tolerability and efficacy profile against relapsed/refractory non-Hodgkin's lymphoma in phase 1 clinical trial [4]. It is currently undergoing phase 2 clinical trials in China [3].
Mechanism Of Action and Pharmacodynamic Effects
PI3Kδ and its downstream target, AKT, are frequently activated in leukemic blasts from patients with B‐cell malignancies or acute myeloid leukemia (AML), and selective inhibitors of the δ isoform show efficacy in certain B-cell malignancies [1-2]. PI3Kδ inhibition is suggested to release leukemia and lymphoma cells from their protective niche by disrupting signals from the lymphoid microenvironment [2].