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CPI-203 

Cat. No.: HY-15846 Purity: 99.38%
Data Sheet SDS Handling Instructions

CPI-203 is a novel potent, selective and cell permeable inhibitor of BET bromodomain, with an IC50 value of appr 37 nM (BRD4 α-screen assay).

For research use only. We do not sell to patients.
CPI-203 Chemical Structure

CPI-203 Chemical Structure

CAS No. : 1446144-04-2

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $88 In-stock
2 mg $60 In-stock
5 mg $100 In-stock
10 mg $180 In-stock
25 mg $400 In-stock
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

CPI-203 is a novel potent, selective and cell permeable inhibitor of BET bromodomain, with an IC50 value of appr 37 nM (BRD4 α-screen assay).

IC50 & Target

IC50: 37 nM (BRD4)

In Vitro

CPI203 inhibits BRD4 in vitro and in cells, but does not affect BRD4 kinase activity in vitro[1]. CPI203 exerts a cytostatic effect in all the 9 MCL cell lines analyzed with GI50 ranging from 0.06 to 0.71 μM, with low cytotoxicity in normal PBMCs from healthy donors. Furthermore, lenalidomide and CPI203, by targeting IRF4 and MYC, efficiently activates the cell death program in MCL cells resistant to bortezomib[2].

In Vivo

BRD4 mediates CTD Ser2 phosphorylation in vivo[1]. In REC-1 tumor-bearing mice, the combination of lenalidomide with CPI203 (2.5 mg/kg, i.p.) synergistically augments the antitumoral properties of each single agent via the abrogation of MYC and IRF4 expression and the induction of apoptosis[2].

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.5006 mL 12.5031 mL 25.0063 mL
5 mM 0.5001 mL 2.5006 mL 5.0013 mL
10 mM 0.2501 mL 1.2503 mL 2.5006 mL
Kinase Assay
[1]

In vitro kinase assays with BRD4, PTEFb, and TFIIH are performed in 20 μL 50 mM Tris, pH 7.5, 5 mM DTT, 5 mM MnCl2, and 5 mM MgCl2 with 10 μCi γ32P ATP (6,000 Ci/mM) and/or 40 μM ATP where indicated. The kinase reactions are incubated for 1 h at 30°C, and then, the proteins are resolved by SDS/PAGE; the extent of phosphorylation is quantitated by a phosphorimager. For kinetic measurements, the quantitated values are plotted on a Lineweaver-Burke plot to calculate Vmax and Km values. When kinase inhibitors are used, appropriate dilutions of the inhibitor are added at the start of the kinase reaction. Mock-treated kinase reactions are treated with equivalent volumes of DMSO. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

MCL primary cells (1.5×105) and cell lines (4×104) are incubated as indicated with lenalidomide and/or PI203. MTT (3-(4,5-dimethylthiazolyl- 2)-2,5-diphenyltetrazolium bromide) reagent is added for 2-6 additional hours before spectrophotometric measurement. Each measurement is made in triplicate. Values are represented using untreated control cells as reference. The GI50 is calculated as the concentration that produced 50% growth inhibition. Combination indexes (CIs) are calculated by using the Calcusyn software version 2.0. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

CB17-severe combined immunodeficiency (SCID) mice are inoculated subcutaneously with 107 cells of the indicated MCL cell line, and monitored for tumor growth and vital parameters as previously described. For lenalidomide and lenalidomide-bortezomib dosing, mice are randomly assigned into cohorts of 3-4 mice each and receive by intraperitoneal injection a twice weekly dose of bortezomib (0.15 mg/kg), a daily dose of lenalidomide (50 mg/kg), the combination of lenalidomide and bortezomib, or an equal volume of vehicle. In the lenalidomide-CPI203 protocol, a total of 22 REC-1 tumor-bearing mice are randomly assigned to cohorts of 5-6 mice, receiving a twice daily intraperitoneal injection of 2.5 mg/kg CPI203, a daily intraperitoneal injection of 50 mg/kg lenalidomide, both agents or an equal volume of vehicle. Between 26 and 29 days post-inoculation, animals are killed according to institutional guidelines and tumor samples are subjected to immunohistochemical staining using primary antibodies against phospho-histone H3, cleaved caspase-3 (5A1E) and MYC (D84C12), IRF4 (M-17) and platelet endothelial cell adhesion molecule-1 (PECAM-1) (M20), CD19 (LE-CD19), Blimp-1 (clone Ros195G/G5), PAX5 (clone 24), CCL3 and CD38, as previously described. Preparations are evaluated using an Olympus DP70 microscope and Cell B Basic Imaging Software. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

399.9

Formula

C₁₉H₁₈ClN₅OS

CAS No.

1446144-04-2

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 47 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
CPI-203
Cat. No.:
HY-15846
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