Ask about this productRelated genes to: IKZF3 Blocking Peptide
- Gene:
- IKZF3 NIH gene
- Name:
- IKAROS family zinc finger 3
- Previous symbol:
- ZNFN1A3
- Synonyms:
- Aiolos
- Chromosome:
- 17q12-q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-23
- Date modifiied:
- 2018-02-13
Related products to: IKZF3 Blocking Peptide
Related articles to: IKZF3 Blocking Peptide
- Targeted protein degradation represents an emerging new drug discovery strategy. Herein, we identified a novel and potent dual-target degrader targeting PARP1 and IKZF3 based on our previously reported PARPi Thioparib. , compound () exerted impressive antiproliferative activities against HR-deficient cancer cells with IC values ranging from 0.006 nM to 39.41 nM. Concurrently, compound displayed potent cell growth inhibitory activities against HR-proficient and clinically used PARPi-resistant cancer cells, with efficacy significantly superior to that of AZD5305. , compound demonstrated excellent tumor growth inhibition (TGI) in the AZD5305-sensitive/-insensitive xenograft model with TGI values of 133.6% and 71.9%, respectively. Collectively, compound may be a powerful therapeutic agent not only for treating PARPi-sensitive tumors but also PARPi-resistant tumors, even HR-proficient tumors. - Source: PubMed
Publication date: 2026/06/30
Zhang XuetaoHe JingLi YaoyaoBao XubinWang XiangyuMiao Ze-HongWang Chang-YunLiu ZhiqingHe Jin-XueWang Pingyuan - Primary cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin lymphomas. Outcomes for patients with advanced-stage disease are suboptimal, as few complete and durable responses are achieved with currently available therapeutic agents. However, improved understanding of oncogenic transcriptional programs in malignant T cells and their engagement with the tumor microenvironment (TME) may unveil therapeutic vulnerabilities. Therefore, we have compiled the largest available scRNA-seq CTCL atlas that includes >2 million skin and blood cells from 116 individual patients. We identified recurrent transcriptional programs in malignant T cells, a subset of which are associated with GATA-3 dependent transcriptional programs, especially in the setting of large cell transformation and advanced-stage disease. Many of the transcriptional programs identified are therapeutically targetable with clinically available agents, including HDAC, XPO1, CDK9, JAK/CSF1R, and IKZF1/IKZF3 antagonists. The CTCL TME is dominated by infiltrating and exhausted effector and cytotoxic T cells that are restrained by a robust infiltrate of regulatory T cells, transcriptionally polarized monocytes/macrophages, and cancer-associated fibroblasts. Collectively, these findings have significant implications for the rationale design of combinatorial strategies targeting immune checkpoints, including PD-1. We have identified transcriptional programs, driven by oncogenic transcription factors, and constituents of the TME as therapeutic vulnerabilities in CTCL, and hope that the CTCL atlas constructed will provide a valuable resource for future studies exploiting these therapeutic vulnerabilities. - Source: PubMed
Publication date: 2026/06/30
Wang ChenguangGeng XiangrongAbdelrahman SuhaibFu YaoKady NerminRauf Mohd AhmarHristov AlexandraTejasvi TrilokrajMurga-Zamalloa CarlosTsoi LamWelch JoshuaFox JenniferCarty Shannon AnnGudjonsson Johann EWilcox Ryan A - The intramuscular fat (IMF) content is an important indicator of meat quality, affecting the sensory properties of meat. IMF is a complex trait with polygenic nature. This research aimed to identify differentially expressed (DE) genes and key transcription factors (TFs) associated with IMF deposition in the liver of two rabbit lines divergently selected for IMF (high-IMF: H and low-IMF: L). We used 48 rabbits (24 H and 24 L) belonging to the 9th generation of selection to determine their liver gene expression levels using 3' RNA sequencing. We found 263 DE genes between H and L lines; 114 upregulated and 149 downregulated in the H line. Among them, over 30 genes were related to lipid metabolism, energy homeostasis, glutathione-purine metabolism, and/or molecule transport that could influence the IMF deposition. Of the 263 DE genes, 175 target genes were predicted for 11 DE TFs through the gene regulatory networks. Notably, three TFs, namely ETV1, NR4A1, and IKZF3 appear to modulate gene expression of several putative targets involved in lipid and energy metabolism (e.g., CREM, GDF15, and NR4A2). Functional analysis of DE genes revealed an overrepresentation of 37 enriched terms, including the PPAR signalling pathway (associated genes: CPT1B, CYP4A6, FABP4, and PLIN2) and other lipid metabolism bioprocesses. Collectively, our results enhance the understanding of the liver-muscle crosstalk that contributes to IMF deposition and improvement of rabbit meat quality. - Source: PubMed
Valdés-Hernández JesúsZubiri-Gaitán AgostinaMartínez-Álvaro MarinaBlasco AgustínHernández Pilar - IKAROS, HELIOS, and AIOLOS are transcription factors predominantly expressed in hematopoietic cells, where they form heteromeric and homodimeric complexes and facilitate transcriptional regulation. IKZF proteins also associate with non-IKZF family proteins, which vary between different immune cell subtypes and their differentiation stages. Heterozygous germline loss-of-function variants in , , and cause IKAROS, HELIOS, and AIOLOS deficiencies, respectively, leading to inborn errors of immunity (IEI). Heterozygous gain-of-function (GOF) variants in result in IKAROS-GOF disease, characterized by autoimmune and allergic manifestations, whereas dominant-negative IKAROS and AIOLOS variants are associated with combined immunodeficiency. Importantly, patients with IKZF-associated IEI exhibit varying degrees of immunodeficiency, immune dysregulation, and occasional malignancies, and so, disease manifestations differ significantly among the variant types. Therefore, each variant often causes phenotypic heterogeneity, which possibly stems from diverse protein complexes formed by IKZF proteins. Besides immunoglobulin supplementation for patients with B cell defects and hematopoietic cell transplantation for severe cases, molecularly targeted therapies have been investigated for treating IKAROS-GOF disease. - Source: PubMed
Publication date: 2025/07/18
Yamashita MotoiMorio Tomohiro - T cell exhaustion has been shown to be a key resistance mechanism to efficacy of T cell engagers (TCE) in multiple myeloma (MM). Mezigdomide, a potent cereblon E3 ligase modulator that targets IKZF1 and IKZF3 simultaneously for proteasomal degradation, has been shown to modulate T cell activity in MM patients. We explored the possibility that targeting IKZF1/IKZF3 could address T cell exhaustion and restore functionality. We conducted extensive transcriptomic and epigenetic profiling on ex vivo generated exhausted T cells, using their autologous activated T cells as a comparison. Our study reveals that IKZF1 and IKZF3 are critical regulators contributing to the development and maintenance of T cell exhaustion. They regulate transcription by directly binding to promoters and enhancers, both proximal and distal, thereby altering transcriptional potential. Increased IKZF1 binding to exhaustion genes after multiple T cell stimulations results in enhancement of transcription, while binding to cytokine genes results in transcription repression. Mezigdomide treatment in exhausted T cells results in decreased expression of exhaustion-related markers, increased proinflammatory cytokine expression, and enhanced target cell killing with Alnuctamab, a B-cell maturation antigen (BCMA) targeting TCE. This study provides crucial mechanistic insights into the roles of IKZF1/IKZF3 in T cell exhaustion, supporting the rationale for combining mezigdomide with TCEs to enhance therapeutic outcomes in MM. - Source: PubMed
Publication date: 2026/05/12
Chiu HsilingZhao JunfeiBasavanhally TaraHsu Chih-ChaoAmatangelo Michael DJain GauravBjorklund Chad CHuang Ting-HsiangChen Lucia YMilne Thomas AGooding SarahParekh SamirGandhi Anita KrithivasOrtiz Estevez MariaHagner Patrick Ryan