IKZF4

IKZF4/Eos is a zinc-finger transcription factor of the Ikaros family that binds GGGAA Ikaros recognition sites and functions as a transcriptional repressor^[1]. In FOXP3⁺ regulatory T cells, Eos directly interacts with Foxp3 and induces chromatin modifications that silence target genes, making IKZF4 relevant to Treg programming, immune tolerance, and gene repression assays^[2]. Mechanistically, IKZF4 belongs to the Treg signature gene set, and Treg-specific epigenetic programs help maintain stable expression of genes such as Ikzf2 and Ikzf4 beyond transient FoxP3 expression^[3]. In disease models, selective Eos deletion in Treg cells caused loss of suppressive function and systemic autoimmunity, supporting IKZF4-focused autoimmune research designs^[4]. Compared with the related isoform IKZF2/Helios, Eos and Helios are both highly expressed in CD4⁺ Treg cells, yet double-deficient models showed unimpaired Treg development and distinct, largely non-overlapping transcriptional programs^[5]. Eos downregulation also controlled reprogramming of an Eos-labile Foxp3⁺ T-helper subset at inflammatory sites^[6]. Outside Treg biology, Eos regulated IL-2 and Th17 production in CD4⁺ conventional T cells and promoted TH2 differentiation through STAT5 activity^[7]^[8]. For experimental applications, the CELMoD degrader BMS-986449 degrades IKZF2/IKZF4 and supports Treg-reprogramming studies in solid tumor models^[9].

References:

[1]. Perdomo J, et al. The Ikaros family protein Eos associates with C-terminal-binding protein corepressors. Eur J Biochem. 2002 Dec;269(23):5885-92. [Content Brief]

[2]. Pan F, et al. Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells. Science. 2009 Aug 28;325(5944):1142-6.

[3]. Ohkura N, et al. Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases. Cell Res. 2020 Jun;30(6):465-474.

[4]. Gokhale AS, et al. Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity. J Autoimmun. 2019 Dec;105:102300.

[5]. Polak K, et al. CD4⁺ regulatory T cells lacking Helios and Eos. Biochem Biophys Res Commun. 2023 Sep 24;674:83-89.

[6]. Sharma MD, et al. An inherently bifunctional subset of Foxp3+ T helper cells is controlled by the transcription factor eos. Immunity. 2013 May 23;38(5):998-1012.

[7]. Rieder SA, et al. Eos Is Redundant for Regulatory T Cell Function but Plays an Important Role in IL-2 and Th17 Production by CD4+ Conventional T Cells. J Immunol. 2015 Jul 15;195(2):553-63.

[8]. Tuazon JA, et al. Eos Promotes TH2 Differentiation by Interacting with and Propagating the Activity of STAT5. J Immunol. 2023 Aug 1;211(3):365-376.

[9]. Ali SR, et al. Nerve Density and Neuronal Biomarkers in Cancer. Cancers (Basel). 2022 Oct 1;14(19):4817.

IKZF4 Inhibitors (2)

IKZF4 관련 제품 (2):

By Type:	Pan (1)

Cat. No.	상품명	효과	Purity

HY-144998

NVP-DKY709	Inhibitor	99.66%
NVP-DKY709 is an orally active and selective IKZF2 molecular glue degrader with the D_max and DC₅₀ of 53% and 4 nM, respectively. In addition, NVP-DKY709 can degrade IKZF4 (DC₅₀: 13 nM) and SALL4 (DC₅₀: 2 nM). NVP-DKY709 exerts anti-tumor activity by binding with CRBN to change conformation and recruit and degrade IKZF2.

HY-173630

BMS-986449	Inhibitor
BMS-986449 is a potent and orally active CELMoD molecular glue and an IKZF2/IKZF4 degrader. BMS-986449 targets the degradation of transcription factors Helios (IKZF2) and Eos (IKZF4) in regulatory T (Treg) cells. BMS-986449 redirects the E3 ubiquitin ligase Cereblon to induce the degradation of Helios and Eos, reprogramming Treg cells and enhancing antitumor immunity. BMS-986449 is promising for research of advanced solid tumors.

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