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Chemical Structure| 1542705-92-9 Chemical Structure| 1542705-92-9

Structure of CB-5083
CAS No.: 1542705-92-9

Chemical Structure| 1542705-92-9

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CB-5083 is a first-in-class, potent, selective, and orally bioavailable inhibitor of the p97 AAA ATPase/VCP, selectively inhibiting p97 through its D2 site with an IC50 of 11 nM.

Synonyms: CB-5083

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Product Details of CB-5083

CAS No. :1542705-92-9
Formula : C24H23N5O2
M.W : 413.47
SMILES Code : O=C(C1=CC=CC2=C1C=C(C)N2C3=NC(NCC4=CC=CC=C4)=C(COCC5)C5=N3)N
Synonyms :
CB-5083
MDL No. :MFCD28963914
InChI Key :RDALZZCKQFLGJP-UHFFFAOYSA-N
Pubchem ID :73051434

Safety of CB-5083

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Related Pathways of CB-5083

DNA

Isoform Comparison

Biological Activity

Target
  • ATPase

    p97 AAA ATPase, IC50:11 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
HEK293T cells 0.73 μM 6 hours CB-5083 caused accumulation of TCR α-GFP in the endoplasmic reticulum, indicating a direct block in ER extraction PMC4941640
A549 cells 2.5 μM 6 hours CB-5083 treatment led to accumulation of K48 poly-ubiquitinated proteins, initially in the cytoplasm and later primarily in the nucleus, indicating that ERAD-independent substrate degradation was also blocked PMC4941640
HCT116 cells 1 μM 8 hours CB-5083 treatment led to significant upregulation of DR5 mRNA and protein, further activating caspase-8 and caspase-3/7, ultimately leading to cell death PMC4941640
BALL1 0.34 μM 72 hours CB-5083 significantly reduced the viability of BALL1 cells with an IC50 of 0.34 μM. PMC5576979
OP1 0.5 μM 15 days CB-5083 significantly reduced the colony formation of OP1 cells by 70% at 0.5 μM. PMC5576979
NALM6 0.5 μM 12 days CB-5083 significantly reduced the colony formation of NALM6 cells by 81% at 0.5 μM. PMC5576979
MC57 cells 5 µM 6 hours To analyze the induction of the unfolded protein response (UPR), results showed that CB-5083 treatment enhanced the UPR in LCMV-infected cells. PMC9715549

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice HCT116 xenograft model Oral 200 mg/kg Once daily for 4 consecutive days CB-5083 caused accumulation of poly-ubiquitin and CHOP in tumor tissue and induced apoptosis, demonstrating antitumor activity PMC4941640
NSG mice Z138C and Jeko-1 xenograft models oral 400 mg/kg/day Once daily for 14 days reduces tumor volume and improves survival PMC6730676
nude mice MDA-231 xenograft model oral 25 mg/kg and 100 mg/kg Single dose CB-5083 significantly inhibited tumor growth and lung metastasis of MDA-231 cells. PMC9980475
mice LCMV infection model oral 40 mg/kg 4 days on, 3 days off, for two weeks To evaluate the effect of CB-5083 on the immune response in LCMV-infected mice, results showed that CB-5083 treatment reduced the cytotoxic T cell response and impaired viral clearance. PMC9715549

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02243917 Advanced Solid Tumors PHASE1 TERMINATED 2017-08-25 HonorHealth Research Institute... More >>, Scottsdale, Arizona, 85258, United States|Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, 90048, United States|University of California San Francisco, San Francisco, California, 94115, United States|University of Colorado, Aurora, Colorado, 80045, United States|Winship Cancer Institute of Emory University, Atlanta, Georgia, 30322, United States|University of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania, 19104, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.42mL

0.48mL

0.24mL

12.09mL

2.42mL

1.21mL

24.19mL

4.84mL

2.42mL

References

 

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