| Name | GMB-475 |
| Description | GMB-475 is a BCR-ABL1 tyrosine kinase degrader based on PROTAC, overcoming BCR-ABL1-dependent drug resistance. GMB-475 targets BCR-ABL1 protein and recruits the E3 ligase Von Hippel Lindau (VHL).resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein |
| In vitro | GMB-475 inhibited the proliferation of certain clinically relevant BCR-ABL1 kinase domain point mutants and further sensitized Ba/F3 BCR-ABL1 cells to inhibition by imatinib, while demonstrating no toxicity toward Ba/F3 parental cells.?Reverse phase protein array analysis suggested additional differences in levels of phosphorylated SHP2, GAB2, and SHC associated with BCR-ABL1 degradation.?Importantly, GMB-475 reduced viability and increased apoptosis in primary CML CD34+ cells, with no effect on healthy CD34+ cells at identical concentrations.?GMB-475 degraded BCR-ABL1 and reduced cell viability in primary CML stem cells.?Together, these findings suggest that combined BCR-ABL1 kinase inhibition and protein degradation may represent a strategy to address BCR-ABL1-dependent drug resistance, and warrant further investigation into the eradication of persistent leukemic stem cells, which rely on neither the presence nor the activity of the BCR-ABL1 protein for survival. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 245 mg/mL (284.25 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (5.8 mM), Sonication is recommended.
|
| Keywords | PROTACs | Inhibitor | inhibit | GMB-475 | GMB475 | GMB 475 | Bcr-Abl1 | Bcr-Abl | BcrAbl | Apoptosis |
| Inhibitors Related | Stavudine | Aceglutamide | Urea | Tamoxifen | Cysteamine hydrochloride | Metronidazole | Citric Acid Triammonium | Formamide | Dimethyl phthalate | Alginic acid | Sodium Molybdate | Sildenafil citrate |
| Related Compound Libraries | Bioactive Compound Library | Ubiquitination Compound Library | Epigenetics Compound Library | Tyrosine Kinase Inhibitor Library | Kinase Inhibitor Library | Angiogenesis related Compound Library | NO PAINS Compound Library | Stem Cell Differentiation Compound Library | Immunology/Inflammation Compound Library | Bioactive Compounds Library Max | Anti-Cancer Compound Library | Transcription Factor-Targeted Compound Library |
United States
