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].
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Summary of Clinical Use Click here for help
Olaptesed pegol (NOX-A12) has reached Phase 2 clinical trial in combination therapies for chronic lymphocytic leukemia (CLL- see NCT01486797 for example). It is also being evaluated as a cell mobilising agent in stem cell transplant patients, and for anti-tumour effects in patients with metastatic pancreatic and colorectal cancers. Olaptesed pegol has been granted orphan drug designation by both the FDA (glioblastoma; FDA link) and EMA (glioma; EMA link).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01486797 NOX-A12 in Combination With Bendamustine and Rituximab in Relapsed Chronic Lymphocytic Leukemia (CLL) Phase 2 Interventional NOXXON Pharma AG