CBL0137 hydrochloride

Research use only, not for human use.

CBL0137 activates p53 and inhibits NF-kB (EC50: 0.37/0.47 μM) in the cell-based p53 and NF-kB reporter assays, respectively. It also suppresses histone chaperone FACT.

CBL0137 (CBL-0137) activates p53 and inhibits NF-kB with EC50s of 0.37 μM and 0.47 μM in the cell-based p53 and NF-kB reporter assays, respectively. It also inhibits histone chaperone FACT (facilitates chromatin transcription complex).(In Vitro):Treatment with CBL0137 hydrochloride leads to complete absence of living cells at concentrations above 2.5 μM. CBL0137 hydrochloride causes a greater reduction in the number of colonies formed of not only MiaPaCa-2 cells when combines with gemcitabine, but also gemcitabine-resistant PANC-1 cells. Treatment of human pancreatic cancer cells with CBL0137 hydrochloride results in a dose dependent reduction of protein and mRNA levels of RRM1 and RRM2. (In Vivo):The CBL0137 hydrochloride monotherapy group and the CBL0137 hydrochloride-gemcitabine combination group samples show large necrotic fields, numerous apoptotic bodies and loss of tumor cells. Sub-optimal doses of 50 to 60 mg/kg CBL0137 hydrochloride causes similar enhancement of gemcitabine antitumor activity as that produced by the maximum tolerated dose (MTD) of 90 mg/kg as indicated by the lack of statistically significant differences among the combination groups. CBL0137 hydrochloride inhibits FACT function through depletion of the pool of active FACT involved in transcription elongation. CBL0137 hydrochloride, given by oral gavage at a nontoxic dose of 30 mg/kg per day on a 5 days on/2 days off schedule, suppresses tumor growth in xenografts of colon (DLD-1), renal cell carcinoma (Caki-1), and melanoma (Mel-7) tumor cell lines and transplanted surgical samples from patients with pancreatic ductal adenocarcinoma.

Treatment with CBL0137 hydrochloride leads to complete absence of living cells at concentrations above 2.5 μM. CBL0137 hydrochloride causes a greater reduction in the number of colonies formed of not only MiaPaCa-2 cells when combines with gemcitabine, but also gemcitabine-resistant PANC-1 cells. Treatment of human pancreatic cancer cells with CBL0137 hydrochloride results in a dose dependent reduction of protein and mRNA levels of RRM1 and RRM2.

The CBL0137 hydrochloride monotherapy group and the CBL0137 hydrochloride-gemcitabine combination group samples show large necrotic fields, numerous apoptotic bodies and loss of tumor cells. Sub-optimal doses of 50 to 60 mg/kg CBL0137 hydrochloride causes similar enhancement of gemcitabine antitumor activity as that produced by the maximum tolerated dose (MTD) of 90 mg/kg as indicated by the lack of statistically significant differences among the combination groups. CBL0137 hydrochloride inhibits FACT function through depletion of the pool of active FACT involved in transcription elongation. CBL0137 hydrochloride, given by oral gavage at a nontoxic dose of 30 mg/kg per day on a 5 days on/2 days off schedule, suppresses tumor growth in xenografts of colon (DLD-1), renal cell carcinoma (Caki-1), and melanoma (Mel-7) tumor cell lines and transplanted surgical samples from patients with pancreatic ductal adenocarcinoma.

CBL0137 | CBL-0137 | CBL 0137 | Curaxin 137

Apoptosis

IL Receptor

FACT|p53|NF-κB

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1197397-89-9

372.88

C21H25ClN2O2

>98% (HPLC)

DMSO : 30 mg/mL. 80.45 mM; H2O : 15.2 mg/mL. 40.76 mM

CC(C)NCCN1C2=C(C=C(C=C2)C(=O)C)C3=C1C=CC(=C3)C(=O)C.Cl

1,1'-(9-(2-((1-Methylethyl)imino)ethyl)-9H-carbazole-3,6-diyl)bisethanone, hydrochloride (1:1)

(-20℃)

With Ice Pack

≥ 2 years