Icotrokinra peptide

Icotrokinra peptide

• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

Batch to batch variation of the purity

Ac-Pen-Asn-Thr-Trp(7-Me)-Lys(Ac)-Pen-Phe(4-amino ethoxy)-2Nal-ThpGly-Glu-Asn-3Pal-Sar-NH2 (Pen1&Pen6 bridge)

13

95.76%

C₉₀H₁₂₀N₂₀O₂₂S₂

1898.2

2763602-16-8

162462321

Synthetic

Powder

Icotrokinra (JNJ-77242113) is a highly potent peptide that selectively targets the IL-23 receptor (IL-23R) and inhibits the IL-23 signaling pathway. It has the potential to be an oral therapy for immune-mediated inflammatory diseases. Icotrokinra binds to the human IL-23R extracellular domain (ECD) with a high affinity (Kd 7.1 pM at 37°C) and to the rat IL-23R ECD with a Kd of 17.5 pM at 37°C. In human PBMCs, Icotrokinra potently and selectively inhibited IL-23-induced STAT3 phosphorylation (IC50 5.6 pM) without impacting IL-12-induced STAT4 phosphorylation. It also inhibited IL-23-induced IFNγ production in NK cells and in whole blood from healthy donors and psoriasis patients with IC50 values of 18.4 pM, 11 pM (median for healthy donors), and 9 pM (median for psoriasis patients), respectively. Inhibition of a panel of potential secondary pharmacodynamic targets was < 50% at 10 μM, confirming its selectivity for IL-23R. Icotrokinra can be used in the study of psoriasis, psoriatic arthritis, inflammatory bowel disease and other immune-mediated inflammatory diseases.

Normally, this peptide will be delivered in lyophilized form and should be stored in a freezer at or below -20 °C. For more details, please refer to the manual:Handling and Storage of Synthetic Peptides

• Fourie AM, Cheng X, Chang L, Greving C, Li X, Knight B, Polidori D, Patrick A, Bains T, Steele R, Allen SJ, Patch RJ, Sun C, Somani S, Bhandari A, Liu D, Huie K, Li S, Rodriguez MA, Xue X, Kannan A, Kosoglou T, Sherlock JP, Towne J, Holland MC, Modi NB. JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans. Sci Rep. 2024 Jul 30;14(1):17515. doi: 10.1038/s41598-024-67371-5. PMID: 39080319; PMCID: PMC11289455.

Trifluoroacetic acid (TFA) has a significant impact on peptides due to its role in the peptide synthesis process.

TFA is essential for the protonation of peptides that lack basic amino acids such as Arginine (Arg), Histidine (His), and Lysine (Lys), or ones that have blocked N-termini. As a result, peptides often contain TFA salts in the final product.

TFA residues, when present in custom peptides, can cause unpredictable fluctuations in experimental data. At a nanomolar (nM) level, TFA can influence cell experiments, hindering cell growth at low concentrations (as low as 10 nM) and promoting it at higher doses (0.5–7.0 mM). It can also serve as an allosteric regulator on the GlyR of glycine receptors, thereby increasing receptor activity at lower glycine concentrations.

In an in vivo setting, TFA can trifluoroacetylate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.