Home Transmembrane Transporters ATPase inhibitor - p97 inhibitor CB-5083 For research use only.

CB-5083

CB-5083 is a potent, selective, and orally bioavailable p97 AAA ATPase inhibitor with IC50 of 11 nM. Phase 1.

CB-5083 Chemical Structure

CB-5083 Chemical Structure

CAS No. 1542705-92-9

Purity & Quality Control

CB-5083 Related Products

Signaling Pathway

ATPase Signaling Pathways

ATPase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A549 Function assay 6 hrs Inhibition of p97 ATPase in human A549 cells assessed as reduction in p62 protein incubated for 6 hrs by immunofluorescence assay, IC50 = 0.49 μM. 26565666
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells assessed as cell viability after 72 hrs by Celltiter-Glo assay, IC50 = 0.68 μM. 26565666
A549 Function assay 6 hrs Inhibition of p97 ATPase in human A549 cells assessed as accumulation of K48 poly-ubiquitinated proteins incubated for 6 hrs by immunofluorescence assay, IC50 = 0.68 μM. 26565666
A549 Function assay 6 hrs Inhibition of p97 ATPase in human A549 cells assessed as accumulation of CHOP poly-ubiquitinated proteins incubated for 6 hrs by immunofluorescence assay, IC50 = 1.03 μM. 26565666
Vero E6 Function assay 48 hrs IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h by immunofluorescence-based assay (detecting the viral NP protein in the nucleus of the Vero E6 cells)., IC50 = 4.89779 μM. 32353859
A549 Function assay 150 mg/kg 2 to 24 hrs Drug uptake in plasma of mouse xenografted with human A549 cells at 150 mg/kg, po measured at 2 to 24 hrs 26565666
A549 Antitumor assay 100 mg/kg Antitumor activity against human A549 cells xenografted in nude SCID beige mouse assessed as tumor growth inhibition at 100 mg/kg, po administered as qd4 on/3 off weekly schedule 26565666
A549 Function assay 150 mg/kg 2 to 24 hrs Drug uptake in human A549 cells xenografted in mouse at 150 mg/kg, po measured at 2 to 24 hrs 26565666
MDA-MB231 Function assay 1 uM 8 hrs Inhibition of p97 in human MDA-MB231 cells assessed as increase in CHOP protein levels at 1 uM after 8 hrs by Western blot analysis 28139929
HCT116 Antitumor assay 75 mg/kg 12 days Antitumor activity against human HCT116 cells xenografted in nude mouse assessed as tumor growth inhibition at 75 mg/kg, po qd for 12 days 26565666
AMO1 Antitumor assay 100 mg/kg Antitumor activity against human AMO1 cells xenografted in nude SCID beige mouse assessed as tumor growth inhibition at 100 mg/kg, po administered as qd4 on/3 off weekly schedule 26565666
AMO1 Antitumor assay 1 mg/kg Antitumor activity against human AMO1 cells xenografted in nude SCID beige mouse assessed as tumor growth inhibition at 1 mg/kg, iv administered twice per week 26565666
Click to View More Cell Line Experimental Data

Biological Activity

Description CB-5083 is a potent, selective, and orally bioavailable p97 AAA ATPase inhibitor with IC50 of 11 nM. Phase 1.
Targets
p97 AAA ATPase [1]
(Cell-free assay)
11 nM
In vitro
In vitro 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. [1]
Kinase Assay ATPase 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 Research Cell lines A549 cells
Concentrations ~40.0 μM
Incubation Time 72 h
Method 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot Bip / XBP1s / PERK / pEIF2α / CHOP p97 p-IRE1α / IRE1α / p-eIF2α / ATF4 26555175
In Vivo
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. [1]
Animal Research Animal Models Nu/Nu nude female mice bearing human HCT 116 colon tumor xenografts
Dosages 75 mg/kg, qd
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02243917 Terminated
Advanced Solid Tumors
Cleave Biosciences Inc.
 October 11 2014 Phase 1
NCT02223598 Terminated
Lymphoid Hematological Malignancies|Relapsed and Refractory Multiple Myeloma
Cleave Biosciences Inc.
 August 25 2014 Phase 1

Chemical Information & Solubility

Molecular Weight 413.47 Formula

C24H23N5O2
CAS No. 1542705-92-9 SDF Download CB-5083 SDF
Smiles CC1=CC2=C(C=CC=C2N1C3=NC4=C(COCC4)C(=N3)NCC5=CC=CC=C5)C(=O)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 82 mg/mL ( (198.32 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 29 mg/mL

Water : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
I am trying to administrate the compound to mice. Does this compound ever dissolve completely?

Answer:
S8101 CB-5083 can be dissolved in 0.5% CMC Na+5% Tween 80 at 30 mg/ml as a suspension for oral gavage.

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