GMB-475 Chemical Properties

Boiling point:

1029.7±65.0 °C(Predicted)

Density 

1.337±0.06 g/cm3(Predicted)

solubility 

DMSO:145.4(Max Conc. mg/mL);168.69(Max Conc. mM)
Ethanol:50.0(Max Conc. mg/mL);58.01(Max Conc. mM)

form 

Solid

pka

13.50±0.46(Predicted)

color 

Light yellow to yellow

InChIKey

ONDVWISBMHHLGZ-XAYQSWBHNA-N

SMILES

C(N1C[C@H](O)C[C@H]1C(=O)NCC1C=CC(C2=C(N=CS2)C)=CC=1)(=O)[C@H](C(C)(C)C)NC(=O)COCCOC1C=CC(C2=NC=NC(NC3C=CC(OC(F)(F)F)=CC=3)=C2)=CC=1 |&1:3,6,24,r|

GMB-475 Usage And Synthesis

Description

GMB-475 acts as a degrader of BCR-ABL 1 tyrosine kinase and as a recruiter of the E3 ligase Von Hippel Lindau (VHL) resulting in ubiquitination and subsequent degradation of oncogenic fusion proteins.

Biological Activity

GMB-475, a BCR-ABL1 Inhibitor Based on PROTAC, Has the Potential to Overcome BCR-ABL1-Dependent Drug Resistance. In both human CML K562 cells and murine Ba/F3 cells expressing BCR-ABL1, GMB-475 induces rapid proteasomal degradation and inhibition of downstream biomarkers. Notably, GMB-475 inhibits the proliferation of certain clinically relevant BCR-ABL1 kinase domain point mutants. GMB-475 reduces viability and increases apoptosis in primary chronic myeloid leukemia CD34+ cells, with no effect on healthy CD34+ cells. Furthermore, GMB-475 degrades BCR-ABL1 and reduces cell viability in primary chronic myeloid leukemia stem cells.

storage

Store at -20°C