olaptesed pegol   Click here for help

GtoPdb Ligand ID: 9674

Synonyms: NOX-A12
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Olaptesed pegol (NOX-A12) is an investigational inhibitor of CXCL12 activity, with a novel mechanism of action [1]. Structurally it is an RNA oligonucleotide in L-configuration (Spiegelmer) conjugated to polyethyleneglycol (PEG). Its sequence is β-L-ribo-[(3'-5')-R-pG-C-G-U-G-G-U-G-U-G-A-U-C-U-A-G-A-U-G-U-A-U-U-G-G-C-U-G-A-UC-C-U-A-G-U-C-A-G-G-U-A-C-G-C], with R being PEG (sequence from the INN record for olaptesed pegol). Chemical synthesis of pegylated Spiegelmers is described by Hoffmann et al. (2011) [2]. Functionally, olaptesed pegol competes with CXCL12 for heparin binding. Once bound to CXCL12, olaptesed pegol causes the release of CXCL12 from stromal cell-surface-bound glycosaminoglycans (GAGs e.g. heparin) and neutralization of the chemokine. This decreases CXCL12 interaction with its cognate receptor CXCR4. Olaptesed pegol was designed to interfere with CXCL12 in the tumour microenvironment, particularly for chronic lymphocytic leukemia, and for cell mobilization. Olaptesed pegol exhibits high binding specificity, low immunogenicity, and structural stability, but it is not orally bioavailable [3].
Bioactivity Comments
Olaptesed pegol interferes with CLL cell chemotaxis and stroma-mediated drug-resistance [1,3].
Selectivity at ligand targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
CXCL12α Primary target of this compound Hs Inhibitor Binding 7.2 pIC50 - 1
⤷ pIC50 7.2 (IC50 6.793x10-8 M) [1]
Description: Inhibition of CXCL12 binding to immobilised heparin in a Biacore competition assay.