CPI-203BET bromodomain inhibitor CAS# 1446144-04-2 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1446144-04-2 | SDF | Download SDF |
PubChem ID | 71291068 | Appearance | Powder |
Formula | C19H18ClN5OS | M.Wt | 399.9 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : ≥ 47 mg/mL (117.53 mM) *"≥" means soluble, but saturation unknown. | ||
SMILES | CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)N)C4=CC=C(C=C4)Cl)C | ||
Standard InChIKey | QECMENZMDBOLDR-AWEZNQCLSA-N | ||
Standard InChI | InChI=1S/C19H18ClN5OS/c1-9-10(2)27-19-16(9)17(12-4-6-13(20)7-5-12)22-14(8-15(21)26)18-24-23-11(3)25(18)19/h4-7,14H,8H2,1-3H3,(H2,21,26)/t14-/m0/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | BET bromodomain inhibitor. Downregulates Myc expression, causes G1 cell cycle arrest and attenuates cell proliferation in human pancreatic neuroendocrine tumors. Arrests the growth of T cell acute lymphoblastic leukemia cells in vitro (EC50 = 91.2 nM). Also enhances the antitumor effect of rapamycin in vitro and attenuates rapamycin induced Akt activation. Orally bioavailable. |
CPI-203 Dilution Calculator
CPI-203 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.5006 mL | 12.5031 mL | 25.0063 mL | 50.0125 mL | 62.5156 mL |
5 mM | 0.5001 mL | 2.5006 mL | 5.0013 mL | 10.0025 mL | 12.5031 mL |
10 mM | 0.2501 mL | 1.2503 mL | 2.5006 mL | 5.0013 mL | 6.2516 mL |
50 mM | 0.05 mL | 0.2501 mL | 0.5001 mL | 1.0003 mL | 1.2503 mL |
100 mM | 0.025 mL | 0.125 mL | 0.2501 mL | 0.5001 mL | 0.6252 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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CPI-203 is a potent, selectivie and competitive small molecule inhibitor of BET bromodomain with a mean GI50 value of 0.23μM in MCL cell lines [1].
As an inhibitor of BET proteins, CPI-203 inhibits BRD4 in vitro and in cells. It inhibits the specific Ser2 phosphorylation of both endogenous BRD4 and exogenous mutant BRD4 (BRD4 FEE-AAA) in vivo, thus blocking the recruitment of BRD4 to chromatin. CPI-203 is shown to suppress cell growth of 9 MCL cell lines. And in REC-1 cells, treatment of CPI-203 causes the effects of IRF4 expression. CPI-203 marginally activates the apoptotic program in these cells. The CPI-203-lenalidomide combination is reported to be a promising strategy in MCL cases refractory to proteasome inhibition [1, 2].
References:
[1] Moros A, Rodríguez V, Saborit-Villarroya I, Montraveta A, Balsas P, Sandy P, Martínez A, Wiestner A, Normant E, Campo E, Pérez-Galán P, Colomer D, Roué G. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Mar 18.
[2] Devaiah BN, Lewis BA, Cherman N, Hewitt MC, Albrecht BK, Robey PG, Ozato K, Sims RJ 3rd, Singer DS. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.
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ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.[Pubmed:26385962]
Genes Dev. 2015 Sep 15;29(18):1915-29.
The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors that serve to restrict HSC differentiation. In the present work, we identify ETS (E-twenty-six)-related gene (ERG) as a critical factor protecting HSCs from differentiation. Specifically, loss of Erg accelerates HSC differentiation by >20-fold, thus leading to rapid depletion of immunophenotypic and functional HSCs. Molecularly, we could demonstrate that ERG, in addition to promoting the expression of HSC self-renewal genes, also represses a group of MYC targets, thereby explaining why Erg loss closely mimics Myc overexpression. Consistently, the BET domain inhibitor CPI-203, known to repress Myc expression, confers a partial phenotypic rescue. In summary, ERG plays a critical role in coordinating the balance between self-renewal and differentiation of HSCs.
The bromodomain and extra-terminal inhibitor CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors.[Pubmed:25299775]
Cell Death Dis. 2014 Oct 9;5:e1450.
Endogenous c-MYC (MYC) has been reported to be a potential pharmacological target to trigger ubiquitous tumor regression of pancreatic neuroendocrine tumors (PanNETs) and lung tumors. Recently inhibitors of bromodomain and extra-terminal (BET) family proteins have shown antitumor effects through the suppression of MYC in leukemia and lymphoma. In this paper, we investigated the antitumor activity of a BET protein bromodomain inhibitor (BETi) CPI203 as a single agent and in combination with rapamycin in human PanNETs. We found that exposure of human PanNET cell lines to CPI203 led to downregulation of MYC expression, G1 cell cycle arrest and nearly complete inhibition of cell proliferation. In addition, overexpression of MYC suppressed the growth inhibition caused by CPI203 and knockdown of MYC phenocopied the effects of CPI203 treatment. These findings indicate that suppression of MYC contributed to the antiproliferative effects of BETi inhibition in human PanNET cells. Importantly, CPI203 treatment enhanced the antitumor effects of rapamycin in PanNET cells grown in monolayer and in three-dimensional cell cultures, as well as in a human PanNET xenograft model in vivo. Furthermore, the combination treatment attenuated rapamycin-induced AKT activation, a major limitation of rapamycin therapy. Collectively, our data suggest that targeting MYC with a BETi may increase the therapeutic benefits of rapalogs in human PanNET patients. This provides a novel clinical strategy for PanNETs, and possibly for other tumors as well.
The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability.[Pubmed:23791182]
Cell. 2013 Jun 20;153(7):1552-66.
Sequencing efforts led to the identification of somatic mutations that could affect the self-renewal and differentiation of cancer-initiating cells. One such recurrent mutation targets the binding pocket of the ubiquitin ligase Fbxw7. Missense FBXW7 mutations are prevalent in various tumors, including T cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. Here, we show that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity. Finally, we demonstrated that small-molecule-mediated suppression of MYC activity leads to T-ALL remission, suggesting an effective therapeutic strategy.