NX-5948
目录号 : GC71231NX-5948是一种具口服活性的蛋白水解靶向嵌合体(PROTAC),是布鲁顿酪氨酸激酶(BTK)的降解剂。
Cas No.:2649400-34-8
Sample solution is provided at 25 µL, 10mM.
NX-5948 is an orally active proteolytic targeting chimera (PROTAC) that is a Bruton’s tyrosine kinase (BTK) degrader[1]. NX-5948 can induce specific BTK protein degradation via the cereblon E3 ligase (CRBN) complex[2]. NX-5948 mediates potent anti-inflammatory activity through BTK degradation, thereby inhibiting B cell activation[3]. In primary human B cells, the half maximal degradation concentration DC50 value of NX-5948 was 0.034nM[4]. NX-5948 can be used to treat B cell malignancies[5].
In vitro, NX-5948 (<1nM) treatment of lymphoma cell lines and peripheral blood mononuclear cells (PBMCs) degraded 50% of cellular BTK[6]. Treatment of BTK-dependent ABC-DLBCL cell line TMD8 cells with NX-5948 (<10nM) for 72h reduced cell viability by 50%[6].
In vivo, oral administration of NX-5948 (10, 30mg/kg) for 18 days to mice model of collagen-induced arthritis (CIA) significantly reduced the mean arthritis score and was well tolerated, and reduced antibody titers and cytokine IL-6 levels[7].
References:
[1] Gao J, Meng C, Yuan V F T. Clinical application of proteolysis targeting chimeras[C]//International Conference on Modern Medicine and Global Health (ICMMGH 2023). SPIE, 2023, 12789: 332-336.
[2] Huynh T, Rodriguez-Rodriguez S, Danilov A V. Bruton Tyrosine Kinase Degraders in B-Cell Malignancies[J]. Molecular Cancer Therapeutics, 2024, 23(5): 619-626.
[3] Huang J, Ma Z, Peng X, et al. Discovery of Novel Potent and Fast BTK PROTACs for the Treatment of Osteoclasts-Related Inflammatory Diseases[J]. Journal of Medicinal Chemistry, 2024, 67(4): 2438-2465.
[4] Rej R K, Allu S R, Roy J, et al. Orally Bioavailable Proteolysis-Targeting Chimeras: An Innovative Approach in the Golden Era of Discovering Small-Molecule Cancer Drugs[J]. Pharmaceuticals, 2024, 17(4): 494.
[5] Mihalic J. First disclosure of Nx-5948, an Oral targeted degrader of Bruton's tyrosine kinase (Btk) for the treatment of B-cell malignancies[C]//266th National Meeting of the American Chemical Society, San Francisco, CA. 2023.
[6] Robbins D W, Noviski M, Rountree R, et al. Nx-5948, a selective degrader of BTK with activity in preclinical models of hematologic and brain malignancies[J]. Blood, 2021, 138: 2251.
[7] Robbins D, Noviski M, Tan M, et al. POS0006 NX-5948, a selective degrader of BTK, significantly reduces inflammation in a model of autoimmune disease[J]. 2021.
NX-5948是一种具口服活性的蛋白水解靶向嵌合体(PROTAC),是布鲁顿酪氨酸激酶(BTK)的降解剂[1]。NX-5948能够通过cereblon E3连接酶(CRBN)复合物诱导特异性BTK蛋白降解[2]。NX-5948通过BTK降解介导有效的抗炎活性,从而抑制B细胞活化[3]。在原代人类B细胞中,NX-5948的半数最大降解浓度 DC50值为0.034nM[4]。NX-5948能够用于治疗B细胞恶性肿瘤[5]。
在体外,NX-5948(<1nM)处理淋巴瘤细胞系和外周血单核细胞(PBMC),降解50%的细胞BTK[6]。NX-5948(<10nM)处理BTK依赖性ABC-DLBCL细胞系TMD8细胞72h,降低了50%的细胞活力[6]。
在体内,NX-5948(10, 30mg/kg)通过口服治疗胶原诱导的关节炎(CIA)模型小鼠18天,显著降低了平均关节炎评分且耐受性良好,降低了抗体滴度和细胞因子IL-6水平[7]。
Cas No. | 2649400-34-8 | SDF | |
分子式 | C42H54N12O5 | 分子量 | 806.96 |
溶解度 | DMSO : 50 mg/mL (61.96 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) | 储存条件 | -20°C |
General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
||
Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
![]() |
1 mg | 5 mg | 10 mg |
1 mM | 1.2392 mL | 6.1961 mL | 12.3922 mL |
5 mM | 0.2478 mL | 1.2392 mL | 2.4784 mL |
10 mM | 0.1239 mL | 0.6196 mL | 1.2392 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet