CBL0137 (hydrochloride)

Description

Curaxins are small molecules that simultaneously activate p53 and inhibit NF-κB without causing detectable genotoxicity. CBL0137 is a water soluble and metabolically stable curaxin that activates p53 with an EC₅₀ value of 0.37 μM and inhibits NF-κB with an EC₅₀ value of 0.47 μM. It functionally inactivates the facilitates chromatin transcription complex, driving the effects on p53 and NF-κB and promoting cancer cell death. CBL0137 has broad anticancer activity in mice when administered orally, eradicates drug-resistant cancer stem cells, and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer.

Uses

CBL0137 Hydrochloride, is an inhibitor of the histone chaperone. It can also activate p53 and inhibits NF-κB with EC50s of 0.37 and 0.47 μM, respectively.

Uses

Curaxins are small molecules that simultaneously activate p53 and inhibit NF-κB without causing detectable genotoxicity. CBL0137 is a water soluble and metabolically stable curaxin that activates p53 with an EC50 value of 0.37 μM and inhibits NF-κB with an EC50 value of 0.47 μM. It functionally inactivates the facilitates chromatin transcription complex, driving the effects on p53 and NF-κB and promoting cancer cell death. CBL0137 has broad anticancer activity in mice when administered orally, eradicates drug-resistant cancer stem cells, and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer.[Cayman Chemical]

Biological Activity

CBL0137 (CBLC137, Curaxin 137) HCl activates p53 and inhibits NF-kB with IC50 of 0.37 μM and 0.47 μM, respectively, in cell experiments. It also inhibits the histone molecular chaperone FACT, which promotes the formation of chromatin transcriptional complexes.

in vitro

cbl0137 was identified as a metabolically stable curaxin activating p53 and inhibiting nf-κb. cbl0137 could functionally inactivate chromatin transcription complex, resulting in the effects on p53 and nf-κb and promoting cancer cell death [1]. it was also found that cbl0137 alone was a potent inducer of apoptosis in pancreatic cancer cell lines and was toxic not only for proliferating bulk tumor cells, but also for pancreatic cancer stem cells [2].

in vivo

in mice, cbl0137 was effective against orthotopic gemcitabine resistant panc-1 model and patient derived xenografts, in which cbl0137 anti-tumor effect related with overexpression of fact. moreover, the combination effects of cbl0137 and gemcitabine might be explained by the ability of cbl0137 to inhibit several transcriptional programs induced by gemcitabine, including nf-kappab response and expression of ribonucleotide reductase [2].

References

1. a. v. gasparian, c. a. burkhart, a. a. purmal, et al. curaxins: anticancer compounds that simultaneously suppress nf-κb and activate p53 by targeting fact. sci.transl.med. 3(95), (2011).2. c. burkhart, d. fleyshman, r. kohrn, et al. curaxin cbl0137 eradicates drug resistant cancer stem cells and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer. oncotarget 5(22), 11038-11053 (2014).