GMB-475

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Chemical Structure| 2490599-18-1 同义名 : -
CAS号 : 2490599-18-1
货号 : A1235114
分子式 : C43H46F3N7O7S
纯度 : 99%+
分子量 : 861.928
MDL号 : MFCD32220458
存储条件：

Pure form Keep in dark place,Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(290.05 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • E3 Ligase
描述 Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of the oncogenic fusion protein BCR-ABL1, the product of a translocation of chromosomes 9 and 22. This fusion results in a constitutively active BCR-ABL1 kinase that drives the overproduction and expansion of white blood cells in the bone marrow, and ultimately crowds out normal cells present in the bone marrow niche. GMB-475 is a degrader of BCR-ABL1 tyrosine kinase based on PROTAC. GMB-475 induced the degradation of BCR-ABL1 and c-ABL1 in the context of both human K562 cells and murine BCR-ABL1 transformed Ba/F3 cells with concomitant inhibition of downstream signaling via the STAT5 pathway, in a dose- and time-dependent fashion (human and murine VHL (Von Hippel Lindau) share >70% identity). In both cases, GMB-475 was capable of inhibiting cell proliferation with an IC50 of approximately 1 μM. Co-treatment of K562 cells with the proteasome inhibitor epoxomicin and GMB-475 restored the levels of BCR-ABL1 and c-ABL1 compared to GMB-475 alone. Dose response titration was performed with BCR-ABL1 transformed Ba/F3 cells for GMB-475 and IC50 value was 1.11 μM. Interestingly, cells bearing a G250E mutation in BCR-ABL1 were particularly susceptible to GMB-475 displaying enhanced antiproliferative activity[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.16mL

0.23mL

0.12mL

5.80mL

1.16mL

0.58mL

11.60mL

2.32mL

1.16mL
参考文献

[1]Burslem GM, Schultz AR, Bondeson DP, et al. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation. Cancer Res. 2019;79(18):4744-4753