GMB-475

Catalog No.S8888 Batch:S888801

Technical Data

Formula	C₄₃H₄₆F₃N₇O₇S
Molecular Weight	861.93	CAS No.	2490599-18-1
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (116.01 mM)
		Ethanol	50 mg/mL (58.0 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

GMB-475 is a proteolysis-targeting chimera (PROTAC) that allosterically targets BCR-ABL1 protein and recruit the E3 ligase Von Hippel-Lindau (VHL), resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein.

Targets

BCR-ABL1 ^[1]

E3 ligase ^[1]

In vitro

GMB-475 induces rapid proteasomal degradation and inhibition of downstream biomarkers, such as STAT5 in both human CML K562 cells and murine Ba/F3 cells expressing BCR-ABL1. GMB-475 inhibits the proliferation of certain clinically relevant BCR-ABL1 kinase domain point mutants and further sensitizes Ba/F3 BCR-ABL1 cells to inhibition by imatinib, while demonstrating no toxicity toward Ba/F3 parental cells.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines K562 cell line, Ba/F3 murine cell lines (Ba/F3 BCR-ABL1 cells, Ba/F3 parental cells) Concentrations 0.001-0.300 μM, 5 μM Incubation Time 3 days, 8 h Method Cell viability assay: Cell lines and patient samples are exposed to dose ranges of GMB-475 (0.001-0.300 μM) and incubated for 3 days at 37°C, 5% CO2 and subjected to a CellTiter 96 AQueous One solution cell proliferation assay. Reverse phase protein arrays (RPPA): K562 cells are treated with DMSO, GMB-475 (5 μM) for 8 h in duplicate, washed twice with PBS and lysed in RPPA lysis buffer.

Cell Assay:^{^[1]}

Cell lines
K562 cell line, Ba/F3 murine cell lines (Ba/F3 BCR-ABL1 cells, Ba/F3 parental cells)
Concentrations
0.001-0.300 μM, 5 μM
Incubation Time
3 days, 8 h
Method
Cell viability assay: Cell lines and patient samples are exposed to dose ranges of GMB-475 (0.001-0.300 μM) and incubated for 3 days at 37°C, 5% CO2 and subjected to a CellTiter 96 AQueous One solution cell proliferation assay. Reverse phase protein arrays (RPPA): K562 cells are treated with DMSO, GMB-475 (5 μM) for 8 h in duplicate, washed twice with PBS and lysed in RPPA lysis buffer.

References

[1] Burslem GM, et al. Cancer Res. 2019 Sep 15;79(18):4744-4753.

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SHIPPING AND STORAGE
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