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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. ✖ |
| References |
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1. Bentebibel SE, Hurwitz ME, Bernatchez C, Haymaker C, Hudgens CW, Kluger HM, Tetzlaff MT, Tagliaferri MA, Zalevsky J, Hoch U et al.. (2019)
A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors. Cancer Discov, 9 (6): 711-721. [PMID:30988166] |
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2. Boyman O, Sprent J. (2012)
The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol, 12 (3): 180-90. [PMID:22343569] |
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3. Charych D, Khalili S, Dixit V, Kirk P, Chang T, Langowski J, Rubas W, Doberstein SK, Eldon M, Hoch U et al.. (2017)
Modeling the receptor pharmacology, pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically-controlled interleukin-2 (IL2) receptor agonist for cancer immunotherapy. PLoS ONE, 12 (7): e0179431. [PMID:28678791] |
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4. Charych DH, Hoch U, Langowski JL, Lee SR, Addepalli MK, Kirk PB, Sheng D, Liu X, Sims PW, VanderVeen LA et al.. (2016)
NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models. Clin Cancer Res, 22 (3): 680-90. [PMID:26832745] |
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5. Doberstein SK. (2019)
Bempegaldesleukin (NKTR-214): a CD-122-biased IL-2 receptor agonist for cancer immunotherapy. Expert Opin Biol Ther, 19 (12): 1223-1228. [PMID:31652082] |
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6. Parisi G, Saco JD, Salazar FB, Tsoi J, Krystofinski P, Puig-Saus C, Zhang R, Zhou J, Cheung-Lau GC, Garcia AJ et al.. (2020)
Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist. Nat Commun, 11 (1): 660. [PMID:32005809] |
