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CAS No.: 2490599-18-1

GMB-475 Catalog No. CSN25549

Synonyms: GMB-475

GMB-475 is a degrader of BCR-ABL1 tyrosine kinase based on PROTAC, overcoming BCR-ABL1-dependent drug resistance. GMB-475 reduced viability and increased apoptosis in primary CML CD34+ cells, with no effect on healthy CD34+ cells at identical concentrations.

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400-920-2911

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靶点选择性

生物活性

实验方案

技术信息

生物活性

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].
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

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.1602 mL
- 5.8009 mL
- 11.6019 mL
- 5 mM
- 0.2320 mL
- 1.1602 mL
- 2.3204 mL
- 10 mM
- 0.1160 mL
- 0.5801 mL
- 1.1602 mL

技术信息

CAS号

2490599-18-1

储存条件

粉末: Keep in dark place,Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C43H46F3N7O7S

运输

蓝冰

分子量

861.93

别名

GMB-475

溶解度

DMSO	100.0 mg/mL (116.0 mM)
Water	Insoluble
Ethanol	50.0 mg/mL (58.0 mM)

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