product name CB-5083
Description: CB-5083 is a novel, potent, selective, first in class and orally bioavailable p97 AAA ATPase inhibitor with IC50 of 11 nM. CB-5083 disrupts cellular protein homeostasis and demonstrates anti-tumor activity in solid and hematological models . CB-5083 causes rapid and sustained accumulation of poly-ubiquitin in tumor xenografts after a single administration. Furthermore, CB-5083 appears to exhibit greater potency over current proteasome inhibitors that further validate targeting p97 and protein homeostasis in the treatment of cancer.
References: J Med Chem. 2015 Dec 24;58(24):9480-97.
413.47
Formula
C24H23N5O2
CAS No.
1542705-92-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 83 mg/mL (200.7 mM)
Water: <1 mg/mL
Ethanol: 13 mg/mL (31.4 mM)
Solubility (In vivo)
0.5% CMC Na+5% Tween 80: 30mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399621/
| In Vitro |
In vitro activity: In A549 cells, CB-5083 causes significant K48 poly-ubiquitinated protein and CHOP accumulation as well as p62 reduction, and kills tumor cells with IC50 of 680 nM. Kinase Assay: Compounds are diluted in DMSO with a 3-fold 10-point serial dilution starting at 10 μM. The assay is done in a 384-well plate with each row as a single dilution series with duplicate of each compound concentration point. In 5 μL total volume, 20 nM p97 hexameric enzyme and 20 μM ATP are added to start the reaction. The plate is sealed and incubated at 37 °C for 15 min after mixing thoroughly in an orbital shaker. Compound dilution, ATP and enzymes addition are conducted with automated liquid handling using the Freedom Evo. ADP Glo reagents 1 and 2 are added according to the manufacturer’s protocol. The luminescence is measured by Envision plate reader as the end point of the reaction. The IC50 of each compound is derived by fitting the luminescence values to a four-parameter sigmoidal curve. Cell Assay: A549 and other tumor cell lines are cultured according to ATCC guidelines. Cells are cultured in black or white, clear-bottomed, tissue culture-treated 384-well plates. Cells are treated with 10-point dose titration of the compound in well duplicates. After a 72 h treatment, CellTiter-Glo is added to the white plates to measure cell viability. Luminescence values are fit to a four-parameter sigmoidal curve to determine IC50 concentrations. |
|---|---|
| In Vivo | In mice bearing human HCT 116 colon tumor xenografts, CB-5083 (75 mg/kg, p.o.) significantly inhibits tumor growth. In mice bearing established human AMO-1 multiple myeloma and A549 lung carcinoma tumor xenografts, CB-5083 (100 mg/kg, p.o.) also results in significant tumor growth inhibition. |
| Animal model | Nu/Nu nude female mice bearing human HCT 116 colon tumor xenografts |
| Formulation & Dosage | Suspended in 0.5% methylcellulose in water; 75 mg/kg, qd; oral administration |
| References | J Med Chem. 2015 Dec 24;58(24):9480-97. |
Related Posts
product name CB-5083
Description: CB-5083 is a novel, potent, selective, first in class and orally bioavailable p97 AAA ATPase inhibitor with IC50 of 11 nM. CB-5083 disrupts cellular protein homeostasis and demonstrates anti-tumor activity in solid and hematological models . CB-5083 causes rapid and sustained accumulation of poly-ubiquitin in tumor xenografts after a single administration. Furthermore, CB-5083 appears to exhibit greater potency over current proteasome inhibitors that further validate targeting p97 and protein homeostasis in the treatment of cancer.
References: J Med Chem. 2015 Dec 24;58(24):9480-97.
413.47
Formula
C24H23N5O2
CAS No.
1542705-92-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 83 mg/mL (200.7 mM)
Water: <1 mg/mL
Ethanol: 13 mg/mL (31.4 mM)
Solubility (In vivo)
0.5% CMC Na+5% Tween 80: 30mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399621/
| In Vitro |
In vitro activity: In A549 cells, CB-5083 causes significant K48 poly-ubiquitinated protein and CHOP accumulation as well as p62 reduction, and kills tumor cells with IC50 of 680 nM. Kinase Assay: Compounds are diluted in DMSO with a 3-fold 10-point serial dilution starting at 10 μM. The assay is done in a 384-well plate with each row as a single dilution series with duplicate of each compound concentration point. In 5 μL total volume, 20 nM p97 hexameric enzyme and 20 μM ATP are added to start the reaction. The plate is sealed and incubated at 37 °C for 15 min after mixing thoroughly in an orbital shaker. Compound dilution, ATP and enzymes addition are conducted with automated liquid handling using the Freedom Evo. ADP Glo reagents 1 and 2 are added according to the manufacturer’s protocol. The luminescence is measured by Envision plate reader as the end point of the reaction. The IC50 of each compound is derived by fitting the luminescence values to a four-parameter sigmoidal curve. Cell Assay: A549 and other tumor cell lines are cultured according to ATCC guidelines. Cells are cultured in black or white, clear-bottomed, tissue culture-treated 384-well plates. Cells are treated with 10-point dose titration of the compound in well duplicates. After a 72 h treatment, CellTiter-Glo is added to the white plates to measure cell viability. Luminescence values are fit to a four-parameter sigmoidal curve to determine IC50 concentrations. |
|---|---|
| In Vivo | In mice bearing human HCT 116 colon tumor xenografts, CB-5083 (75 mg/kg, p.o.) significantly inhibits tumor growth. In mice bearing established human AMO-1 multiple myeloma and A549 lung carcinoma tumor xenografts, CB-5083 (100 mg/kg, p.o.) also results in significant tumor growth inhibition. |
| Animal model | Nu/Nu nude female mice bearing human HCT 116 colon tumor xenografts |
| Formulation & Dosage | Suspended in 0.5% methylcellulose in water; 75 mg/kg, qd; oral administration |
| References | J Med Chem. 2015 Dec 24;58(24):9480-97. |