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NX-5948

目录号 : GC71231

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。

NX-5948 Chemical Structure

Cas No.:2649400-34-8

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥24,000.00
现货
1mg
¥3,220.00
现货
5mg
¥10,000.00
现货

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Sample solution is provided at 25 µL, 10mM.

Description

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]

化学性质

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
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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
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