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Synonyms: NKTR-214 | NKTR214
Compound class:
Peptide or derivative
Comment: Bempegaldesleukin (NKTR-214) is an engineered variant of human interleukin-2 [4] in which Ala1 has been removed and Cys125 is substituted by Ser. The peptide is produced in E. coli and an average of 6 lysine residues are N6 substituted with [(2,7-bis{[methylpoly(oxyethylene)]carbamoyl}-9H-fluoren-9-yl)methoxy]carbonyl (PEG-Lys). In the PEG-bound form the IL-2 is inactive, but In vivo the PEG chains are released slowly which provides a more controlled release of active IL-2 peptide [4] (the IL-2 conjugates with 1 or 2 PEG chains are the most biologically active conjugates [3]). This prodrug strategy mitigates against the severe side effects which limit maximal dosing of parental aldesleukin.
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. ✖ |
| Immunopharmacology Comments |
| Bempegaldesleukin is an investigational immuno-oncology agent [1,5]. It acts as a CD122 (IL-2 receptor β)-preferential IL-2 pathway agonist and is proposed to stimulate the growth of CD8+ effector T cells and natural killer (NK) cells [2,6] which are then mobilised to the tumour micro-environment where they enable an anti-tumour immune response [4]. This mechanism is applicable across a wide range of solid tumour types. As the PEG residues are located within the IL-2Rα binding site of the ligand, the affinity for IL-2Rαβγ (on Tregs) is reduced by a greater extent than the affinity for heterodimeric IL-2Rβγ complexes. This affinity switch favours activation of the IL-2Rβγ receptors on tumour-resident CD8+ T cells and NK cells. Bempegaldesleukin exhibits powerful synergistic anti-tumour efficacy when combined with checkpoint blockade. |
