赛度替尼 T2487

Product Introduction
Bioactivity


英文名: Cerdulatinib

描述: Cerdulatinib (PRT2070) 是一种选择性 Tyk2抑制剂，IC50为 0.5 nM。它是 JAK 和 SYK 的双抑制剂，抑制JAK1、2、3 和SYK 的IC50分别为12、6、8 和 32。

细胞实验: Cerdulatinib is dissolved in DMSO. TMD8 cells are transfected with constructs of WT BTK or BTKC481S mutants using kit V, Program U-13 on Amaxa Nucleofector. After transfection, the cells are co-cultured with NKTert cells in a 24-well plate for 24 hrs for recovery. Ibrutinib, cerdulatinib and vehicle (DMSO) are then added into the transfected TMD8 cells and cellular viability is determined with MuseTM Count & Viability kit using Muse Cell Analyzer. The cell survival is determined by flow cytometry using the Annexin V/7-AAD Apoptosis Detection Kit I on freshly isolated CLL cells.

体外活性: Cerdulatinib exhibits an inhibitory effect on 60 CLL with IC50 ranging from 0.37 to 10.02 μM. Cerdulatinib induces apoptosis in CLL in association with MCL-1 down-regulation and PARP cleavage. Cerdulatinib (2 μM) is able to overcome the support of the microenvironment and induces cell death of CLL. Cerdulatinib (250-500 nM) blocks proliferation of ibrutinib-sensitive and ibrutinib-resistant primary CLL cells. Cerdulatinib also blocks proliferation of both ibrutinib-sensitive and ibrutinib-resistant primary CLL cells as well as BTKC481S-transfected cell lines, and blocks BCR and JAK-STAT signaling pathways. Furthermore, inhibition of SYK and JAK by cerdulatinib translates to downstream inhibition of AKT and ERK. Cerdulatinib inhibits the activity of NF-kB pathway[1]. PRT062070 reduces the ability of stimulated B cells to upregulate cell-surface expression of the early activation marker CD69 (IC50=0.11 μM). PRT062070 exhibits differential potency against cytokine JAK/STAT signaling pathways. PRT062070 (1 or 3 μM) induces apoptosis in BCR-signaling competent NHL cell lines[2]. Cerdulatinib demonstrates inhibitory activity against both ABC and GCB subtypes of DLBCL cells. Cerdulatinib also induces apoptosis in both GCB and ABC subtypes of DLBCL cell lines via caspase 3 and PARP cleavage. And cerdulatinib blocks cell cycle in both ABC and GCB subtypes of DLBCL via inhibition of RB phosphorylation and down-regulation of cyclin E. Cerdulatinib induces cell cycle arrest and apoptosis under the condition of BCR stimulation in all DLBCL cell lines. Besides, cerdulatinib blocks JAK/STAT and BCR signaling in both ABC and GCB DLBCL cell lines. Cerdulatinib induces cell death in primary human DLBCL samples[3]. Cerdulatinib inhibits BCR-induced signals in a dose-dependent manner and most strongly between 0.3 to 1 μM. and particularly in IGHV-unmutated samples with greater BCR signaling capacity and response to IL4, or samples expressing higher levels of sIgM, CD49d+, or ZAP70+. Cerdulatinib overcomes anti-IgM, IL4/CD40L, or NLC-mediated protection by preventing upregulation of MCL-1 and BCL-XL; however, BCL-2 expression is unaffected. Moreover, cerdulatinib synergizes with venetoclax in vitro to induce greater apoptosis than either drug alone in samples treated with IL4/CD40L[4].

体内活性: PRT062070 (0.5 mg/kg) causes a nonstatistically significant trend toward reduced ankle inflammation, whereas significant reductions in inflammation are achieved with the 1.5, 3, and 5 mg/kg doses. Besides, PRT062070 also affects anticollagen antibody formation. PRT062070 (15 mg/kg) suppresses upregulation of splenic B-cell surface CD80/86 and CD69, and inhibits BCR signaling and activation in the spleen after oral dosing in mice[2].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : ~20 mg/mL (44.9 mM)


关键字: Syk | Spleen tyrosine kinase | inhibit | JAK | PRT 2070 | PRT 062070 | Inhibitor | Cerdulatinib | Janus kinase | PRT-062070 | PRT-2070

相关产品: HNMPA-(AM)3 | Baricitinib | ZAP-180013 | Filgotinib | Tyrphostin AG30 | Delgocitinib | ST271 | TAK-659 hydrochloride | NVP-BSK805 2HCl (1092499-93-8(free base)) | Hypericin

相关库: Drug Repurposing Compound Library | Anti-Cancer Compound Library | Anti-Cancer Drug Library | Kinase Inhibitor Library | Inhibitor Library | Anti-Cancer Clinical Compound Library | Epigenetics Compound Library | Anti-Cancer Active Compound Library | Tyrosine Kinase Inhibitor Library | Hematonosis Compound Library

赛度替尼 T2487信息由TargetMol中国为您提供，如您想了解更多关于赛度替尼 T2487报价、型号、参数等信息，欢迎来电或留言咨询。

注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途