itk inhibitor 2

ITK inhibitor 2 (compound 4)是一种高效和选择性 ITK 抑制剂，IC50= 2 nM。

PF-06465469 是一种共价 ITK 抑制剂（IC₅₀ = 2 nM），同时抑制 BTK。PF-06465469 可抑制 CXCL12 介导的细胞迁移，降低 PD-1 和 LAG-3 表达，在白血病及 T 细胞淋巴瘤研究中具有良好应用前景。

PRN694 shows extended target residence time on ITK and RLK, enabling durable attenuation of effector cells in vitro and in vivo. PRN694 is an irreversible, highly selective, and effective covalent interleukin-2-inducible T-cell kinase (ITK) and resting ly

Modzatinib (ITKkinase-IN-1) (compound I) 是一种针对ITK激酶的抑制剂 (IC50=8 nM，Jurkat 细胞)，适合用于研究炎症性疾病。在hPBMC细胞中，Modzatinib 对JAK3的IC50为23 nM（基于IL-2/pSTAT5水平），但对JAK2不具有抑制效果。

GSK-2250665A 是一种白介素-2 可诱导的 T 细胞激酶 (Itk) 抑制剂，其结合亲和力为 pKi = 9.2。GSK-2250665A 对 Itk 显示出显著选择性，相较于 Aurora B 激酶和布鲁顿酪氨酸激酶 (Btk)，pIC50 分别为 6.4 和 6.5，对其他激酶活性有限。同时，GSK-2250665A 抑制外周血单核细胞 (PBMCs) 中干扰素-γ (IFNγ) 产生，是研究 T 细胞受体信号及免疫调控的高度选择性化学探针。

CTA 056 是白细胞介素-2 诱导的 T 细胞激酶（ITK）抑制剂，抑制小鼠 MOLT-4 异种移植肿瘤的生长，诱导 Jurkat 细胞凋亡，可用于研究自身免疫性疾病和T细胞恶性肿瘤。

Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity. In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1]. In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1]. Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.

ITK/TRKA-IN-1 is a chemical compound that functions as a dual inhibitor of IL-2-inducible T-cell kinase (ITK) and tropomyosin receptor kinase A (TRKA). With an IC50 value of 1.0 nM, it effectively inhibits the activity of ITK, while demonstrating a remarkable 96% inhibition of TRKA.

BAY 61-3606 (Syk inhibitor IV) 是一种具有口服活性的，ATP 竞争性的可逆选择性Syk 抑制剂。它作用于乳腺癌细胞，通过下调 Mcl-1 促进 TRAIL 诱导的细胞凋亡。它降低神经母细胞瘤细胞中的 ERK1/2 和 Akt 磷酸化，也降低 K-rn 细胞裂解物中 Syk 磷酸化。

ITK inhibitor 6 是选择性的、有效的 ITK 抑制剂，能够作用于 ITK (IC50: 4 nM)、BTK (IC50: 133 nM)、JAK3 (IC50: 320 nM)、EGFR (IC50: 2360 nM)、LCK (IC50: 155 nM)。ITK inhibitor 6 对 PLCγ1 和 ERK1/2 的磷酸化具有抑制作用，表现出抗增殖效果。