GMB-475
- CAS No.
- 2490599-18-1
- Chemical Name:
- GMB-475
- Synonyms
- GMB-475;GMB-475 ，S8888;GMB-475, 10 mM in DMSO;Bcr-Abl,GMB-475,PROTACs,GMB 475,Apoptosis,Inhibitor,inhibit,GMB475;(2S)-1-((R)-3,3-dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide;(2S,4R)-1-((S)-3,3-Dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
- CBNumber:
- CB58379743
- Molecular Formula:
- C43H46F3N7O7S
- Molecular Weight:
- 861.94
- MDL Number:
- MOL File:
- 2490599-18-1.mol
| 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| |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|---|---|
| Signal word | Warning |
| Hazard statements | H302-H315-H319-H335 |
| Precautionary statements | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
GMB-475 price
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Ambeed | A1235114 | (2S,4R)-1-((S)-3,3-Dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 98% | 2490599-18-1 | 1mg | $77 | 2021-12-16 | Buy |
| Ambeed | A1235114 | (2S,4R)-1-((S)-3,3-Dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 98% | 2490599-18-1 | 5mg | $153 | 2021-12-16 | Buy |
| Ambeed | A1235114 | (2S,4R)-1-((S)-3,3-Dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 98% | 2490599-18-1 | 10mg | $238 | 2021-12-16 | Buy |
| Ambeed | A1235114 | (2S,4R)-1-((S)-3,3-Dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 98% | 2490599-18-1 | 25mg | $309 | 2021-12-16 | Buy |
| Ambeed | A1235114 | (2S,4R)-1-((S)-3,3-Dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 98% | 2490599-18-1 | 50mg | $402 | 2021-12-16 | Buy |
GMB-475 Chemical Properties,Uses,Production
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.
Uses
GMB-475 is a potent BCR-ABL1 PROTAC based on Von Hippel-Lindau (VHL). GMB-475 targets the nutmeg pocket of ABL1 in an ectopic manner and degrades BCR-ABL1 protein through the ubiquitin proteasome pathway. GMB-475 inhibits the proliferation of human K562 cells and mouse Ba/F3 cells, and is used for the study of chronic myeloid leukemia. (Blue: VHL ligand (HY-125845); Black: Linker; Pink: BCR-ABL1 ligand (HY-11007))[1][2].
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.
in vivo
GMB-475 (5 mg/kg; once every two days; 10 days; i.p.) improves chronic myeloid leukemia in mice with BCR::ABL1 mutant by targeted degradation of BCR-ABL1b and combined with dasatinib (HY-10181)[2].
| Animal Model: | 8-week-old Balb/c mice were injected with Ba/F3-MG-p210-Luc cells via tail vein to establish a chronic myeloid leukemia (CML) mouse model[2]. |
| Dosage: | 5 mg/kg |
| Administration: | Intraperitoneal injection (i.p.); once every two days; 10 days |
| Result: | Showed a trend of reducing the tumor burden and prolonging the survival of the CML mouse model. |
IC 50
STAT5; VHL; Bcr-Abl
storage
Store at -20°C
References
[1] Burslem GM, et al. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation. Cancer Res. 2019 Sep 15;79(18):4744-4753. DOI:10.1158/0008-5472.CAN-19-1236
[2] Ye W, et al. The proteolysis targeting chimera GMB-475 combined with dasatinib for the treatment of chronic myeloid leukemia with BCR::ABL1 mutants. Front Pharmacol. 2022 Oct 3;13:931772. DOI:10.3389/fphar.2022.931772
GMB-475 Preparation Products And Raw materials
Raw materials
Preparation Products
GMB-475 Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Hubei Chuchang Biotech Co., Ltd. | +undefined15623860702 | info@chuchangbiotech.com | China | 202 | 58 |
| TargetMol Chemicals Inc. | +17819995354 | marketing@targetmol.com | United States | 32302 | 58 |
| InvivoChem | +1-708-310-1919 +1-13798911105 | sales@invivochem.cn | United States | 6391 | 58 |
| Nantong HI-FUTURE Biology Co., Ltd. | +undefined18051384581 | sales@chemhifuture.com | China | 3135 | 58 |
| TargetMol Chemicals Inc. | support@targetmol.com | United States | 38672 | 58 | |
| Jilin Chinese Academy of Sciences-yanshen Technology | +undefined18143011203 | info@chemextension.com | China | 42056 | 58 |
| Aladdin Scientific | tp@aladdinsci.com | United States | 57505 | 58 | |
| Wuhan Jingkang en Biomedical Technology Co., Ltd | +8613720134139 | orders@jknbiochem.com | China | 5221 | 58 |
| Shanghai YuanQi Biotechnology Co., Ltd. | +86-2332782371 +86-18120098618 | sales@adobechem.com | China | 1250 | 50 |
| Changzhou Chenhong Biotechnology Co., Ltd. | 0519-85788828 13775037613 | sales@chemrenpharm.com | China | 3907 | 58 |
