P001 The biomarker profile of PTG-200, an oral peptide antagonist of IL-23 receptor, tracks with efficacy in a preclinical model of IBD

Cheng, Xiaoli; Taranath, Roopa; Mattheakis, Larry; Bhandari, Ashok; Liu, D.

doi:10.1093/ecco-jcc/jjx002.128

Cited by 3 publications

(2 citation statements)

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“…In fact, according to a prior genome-wide association study, rs10889677 demonstrated a favorable link with IBD and might subsequently make the condition worse clinically [ 27 ]. Additionally, IL23R has just recently been discussed as a potential IBD treatment [ 36 , 37 ]. The activity of the IL23 signaling pathway could be inhibited by specific binding of the oral peptide (PTG-200) to the IL23R , which would subsequently influence JAK2 and TYK2 activation and perhaps result in abnormal STAT3 and STAT4 expression.…”

Section: Discussionmentioning

confidence: 99%

Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer

Razali

Ali

Nawawi

et al. 2022

IJMS

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Chronic relapsing inflammatory bowel disease is strongly linked to an increased risk of colitis-associated cancer (CAC). One of the well-known inflammatory carcinogenesis pathways, phosphatidylinositol 3-kinase (PI3K), was identified to be a crucial mechanism in long-standing ulcerative colitis (UC). The goal of this study was to identify somatic variants in the cytokine-induced PI3K-related genes in UC, colorectal cancer (CRC) and CAC. Thirty biopsies (n = 8 long-standing UC, n = 11 CRC, n = 8 paired normal colorectal mucosa and n = 3 CAC) were subjected to targeted sequencing on 13 PI3K-related genes using Illumina sequencing and the SureSelectXT Target Enrichment System. The Genome Analysis Toolkit was used to analyze variants, while ANNOVAR was employed to detect annotations. There were 5116 intronic, 355 exonic, 172 untranslated region (UTR) and 59 noncoding intronic variations detected across all samples. Apart from a very small number of frameshifts, the distribution of missense and synonymous variants was almost equal. We discovered changed levels of IL23R, IL12Rß1, IL12Rß2, TYK2, JAK2 and OSMR in more than 50% of the samples. The IL23R variant in the UTR region, rs10889677, was identified to be a possible variant that might potentially connect CAC with UC and CRC. Additional secondary structure prediction using RNAfold revealed that mutant structures were more unstable than wildtype structures. Further functional research on the potential variants is, therefore, highly recommended since it may provide insight on the relationship between inflammation and cancer risk in the cytokine-induced PI3K pathway.

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Section: Discussionmentioning

confidence: 99%

Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer

Razali

Ali

Nawawi

et al. 2022

IJMS

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“…PTG-200 is a new SMDs that antagonizes the IL-23 receptor (IL-23R). A phase I study has shown its efficacy in ameliorating colitis in rat models and a phase II trial for CD is currently recruiting patients (40).…”

Section: Current Drug Targets and Innovative Therapiesmentioning

confidence: 99%

Innovative, complementary and alternative therapy in inflammatory bowel diseases: A broad 2020s update

Masi

Ciuffini²,

Petito³

et al. 2022

Front. Gastroenterol.

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Inflammatory bowel diseases (IBD) are chronic disabling conditions with a complex and multifactorial etiology, which is still not completely understood. In the last 20 years, anti-TNF-α antagonists have revolutionized the treatment of IBD, but many patients still do not respond or experience adverse events. Therefore, new biological therapies and small molecules, targeting several different pathways of gut inflammation, have been developed of which some have already been introduced in clinical practice while many others are currently investigated. Moreover, therapeutic procedures such as leukocytapheresis, fecal microbiota transplant and stem cell transplantation are currently being investigated for treating IBD. Lastly, complementary and alternative medicine has become a field of interest for gastroenterologist to reduce symptom burden in IBD patients. In this comprehensive and updated review, a novel classification of current and developing drugs is provided.

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Targeting the Interleukin 23 Pathway in Inflammatory Bowel Disease

Bourgonje,

Ungaro,

Mehandru

et al. 2024

Gastroenterology

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P001 The biomarker profile of PTG-200, an oral peptide antagonist of IL-23 receptor, tracks with efficacy in a preclinical model of IBD

Cited by 3 publications

References 0 publications

Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer

Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer

Innovative, complementary and alternative therapy in inflammatory bowel diseases: A broad 2020s update

Targeting the Interleukin 23 Pathway in Inflammatory Bowel Disease

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