CBL0137 hydrochloride

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

Product information

CAS Number: 1197397-89-9

Molecular Weight: 372.89

Formula: C21H25ClN2O2

Synonym:

CBL-C137 hydrochloride

Curaxin-137 hydrochloride

Chemical Name: 1-(6-acetyl-9-{2-[(propan-2-yl)amino]ethyl}-9H-carbazol-3-yl)ethan-1-one; chlorohydrogen

Smiles: Cl.CC(C)NCCN1C2=CC=C(C=C2C2=CC(=CC=C12)C(C)=O)C(C)=O

InChiKey: IXRKBBVMDMKAEB-UHFFFAOYSA-N

InChi: InChI=1S/C21H24N2O2.ClH/c1-13(2)22-9-10-23-20-7-5-16(14(3)24)11-18(20)19-12-17(15(4)25)6-8-21(19)23;/h5-8,11-13,22H,9-10H2,1-4H3;1H

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 25 mg/mL (67.04 mM; Need ultrasonic). H2O : 10 mg/mL (26.82 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

References:

1. Gasparian AV,etal.Curaxins: anticancer compounds that simultaneously suppress NF-κB and activate p53 by targeting FACT.Sci Transl Med. 2011 Aug 10;3(95):95ra74.
2. Burkhart C,etal.Curaxin CBL20137 eradicates drug resistant cancer stem cells and potentiates efficacy of gemcitabine in preClinicalal models of pancreatic cancer.Oncotarget. 2014 Nov 30;5(22):11038-53.
3. Barone TA,etal.Anticancer drug candidate CBL20137, which inhibits histone chaperone FACT, is efficacious in preClinicalal orthotopic models of temozolomide-responsive and -resistant glioblastoma.Neuro Oncol. 2017 Feb 1;19(2):186-196.

Products are for research use only. Not for human use.