1. Cell Cycle/DNA Damage
    Epigenetics
  2. Polo-like Kinase (PLK)
    Epigenetic Reader Domain

BI 2536 

Cat. No.: HY-50698 Purity: 99.19%
Data Sheet SDS Handling Instructions

BI 2536 is a potent and selective inhibitor of Plk1 with IC50 of 0.83 nM, and is also a potent inhibitor of BRD4 with IC50 of 25 nM.

For research use only. We do not sell to patients.
BI 2536 Chemical Structure

BI 2536 Chemical Structure

CAS No. : 755038-02-9

Size Price Stock Quantity
10 mM * 1 mL in DMSO $126 In-stock
5 mg $110 In-stock
10 mg $198 In-stock
50 mg $528 In-stock
100 mg $856 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

BI 2536 is a potent and selective inhibitor of Plk1 with IC50 of 0.83 nM, and is also a potent inhibitor of BRD4 with IC50 of 25 nM.

IC50 & Target

IC50: 0.83 nM (Plk1), 3.5 nM (Plk2/Snk), 9 nM (Plk3/Fnk)[1]
IC50: 25 nM (BRD4)[2]

In Vitro

Exceeding a 100-fold concentration range starting at 10 nM, BI 2536 causes HeLa cells to accumulate with a 4N DNA content, indicative of a cell-cycle block in either G2 phase or mitosis. In addition to HeLa cells, BI 2536 potently inhibits the proliferation of a panel of 32 human cancer cell lines, representing diverse organ derivations (including carcinomas of the breast, colon, lung, pancreas, and prostate, melanomas, and hematopoietic cancers) and varied patterns of tumor suppressor or oncogene mutations (including RB1, TP53, PTEN, andKRAS status). The half-maximal effective concentration (EC50) values in this cell panel ranged 2-25 nM, whereas a concentration of 100 nM of BI 2536 is typically sufficient for inducing a complete mitotic arrest. The proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells is blocked at EC50values ranging 12-31 nM, indicating a comparable sensitivity of cycling nontransformed cells to BI 2536[3].

In Vivo

BI 2536 (40-50 mg/kg, i.v.) blocks the growth of human cancer xenografts in immunodeficient, nu/nu mice. Consecutive cycles of 40-50 mg/kg BI 2536 given i.v. once or twice per week are found to be highly efficacious in diverse xenograft models, such as the HCT 116 colon cancer with complete tumor suppression with the twice per week schedule (treated versus the control (T/C) value 0.3%) and a T/C value of 16% with once per week treatment; both schedules are well-tolerated, as judged by clinical signs and absence of major body-weight changes[3].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02211833 Boehringer Ingelheim Carcinoma, Non-Small-Cell Lung October 2006 Phase 1
NCT02211872 Boehringer Ingelheim Neoplasms August 2004 Phase 1
NCT02211859 Boehringer Ingelheim Neoplasms August 2004 Phase 1
NCT00701766 Boehringer Ingelheim Leukemia, Myeloid, Acute October 2006 Phase 2
NCT00376623 Boehringer Ingelheim Carcinoma, Non-Small-Cell Lung July 2006 Phase 2
NCT02215044 Boehringer Ingelheim Pancreatic Neoplasms June 2007 Phase 1
NCT00706498 Boehringer Ingelheim Prostatic Neoplasms September 2006 Phase 2
NCT00412880 Boehringer Ingelheim Carcinoma, Small Cell January 2007 Phase 2
NCT00243087 Boehringer Ingelheim Lymphoma July 2005 Phase 1
NCT00710710 Boehringer Ingelheim Pancreatic Neoplasms August 2006 Phase 2
NCT00526149 European Organisation for Research and Treatment of Cancer - EORTC Breast Cancer|Endometrial Cancer|Head and Neck Cancer|Melanoma (Skin)|Ovarian Cancer|Sarcoma July 2007 Phase 2
NCT02211833 Boehringer Ingelheim Carcinoma, Non-Small-Cell Lung October 2006 Phase 1
NCT02211872 Boehringer Ingelheim Neoplasms August 2004 Phase 1
NCT02211859 Boehringer Ingelheim Neoplasms August 2004 Phase 1
NCT00701766 Boehringer Ingelheim Leukemia, Myeloid, Acute October 2006 Phase 2
NCT00376623 Boehringer Ingelheim Carcinoma, Non-Small-Cell Lung July 2006 Phase 2
NCT02215044 Boehringer Ingelheim Pancreatic Neoplasms June 2007 Phase 1
NCT00706498 Boehringer Ingelheim Prostatic Neoplasms September 2006 Phase 2
NCT00412880 Boehringer Ingelheim Carcinoma, Small Cell January 2007 Phase 2
NCT00243087 Boehringer Ingelheim Lymphoma July 2005 Phase 1
NCT00710710 Boehringer Ingelheim Pancreatic Neoplasms August 2006 Phase 2
NCT00526149 European Organisation for Research and Treatment of Cancer - EORTC Breast Cancer|Endometrial Cancer|Head and Neck Cancer|Melanoma (Skin)|Ovarian Cancer|Sarcoma July 2007 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.9170 mL 9.5850 mL 19.1699 mL
5 mM 0.3834 mL 1.9170 mL 3.8340 mL
10 mM 0.1917 mL 0.9585 mL 1.9170 mL
Kinase Assay
[3]

Enzyme activity assays for Plk1, Plk2, and Plk3 are performed in the presence of serially diluted inhibitor (BI 2536) with 20 ng of Recombinant kinase and 10 mg casein from bovine milk as the substrate. Kinase reactions are performed in a final volume of 60 mL for 45 min at 30°C (15 mM MgCl2, 25 mM MOPS [pH 7.0], 1 mM DTT, 1% DMSO, 7.5 mM ATP, 0.3 mCi γ-P33-ATP). Reactions are terminated by the addition of 125 mL of ice-cold 5% TCA. After transfer of the precipitates to Multi-Screen mixed ester cellulose filter plates, plates are washed with1%TCA and quantified radiometrically. Dose-response curves are used for calculating IC50 values[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[3]

BI 2536 is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO 0.1%) before use[3].

Cell proliferation assays are performed by incubation in the presence of various concentrations of BI 2536 (10 nM-1 μM) for 72 hr, and cell growth is assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. Effective concentrations at which cellular growth is inhibited by 50% (EC50) are extrapolated from the dose-response curve fit[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[3]

BI 2536 is formulated in hydrochloric acid (0.1 N), diluted with 0.9% NaCl (Mice)[3].

Mice[3]
Female BomTac:NMRI-Foxn1nu mice are grafted subcutaneously with HCT 116 colon-carcinoma, NCI-H460, or A549 lung-carcinoma cells by subcutaneous injection, respectively, of 2×106, 1×106, and 1×107 cells into the flank of each mouse. When tumors reached a volume of approximately 50 mm3, animals are pair-matched into treatment and control groups of ten mice each. In regression experiments, treatment is not initiated until the mean tumor volume reached 500 mm3. BI 2536 is injected intravenously into the tail vein at the indicated dose and schedule. The administration volume is 10 mL per kg body weight. Tumor volumes are determined three times a week with a caliper. The results are converted to tumor volume (mm3) by the following formula: length×width2×π/6. The weight of the mice is determined as an indicator of tolerability on the same days. For statistical analysis, the treatment group is compared with the vehicle control group in a one-sided (decreasing) exact Wilcoxon test. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

521.65

Formula

C₂₈H₃₉N₇O₃

CAS No.

755038-02-9

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

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

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BI 2536
Cat. No.:
HY-50698
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