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| Targets |
BI2536-PEG2-Halo targets PLK1 (Polo-like kinase 1), a serine/threonine kinase essential for mitotic entry, centrosome maturation, bipolar spindle formation, and cytokinesis. PLK1 is overexpressed in many cancers and is a validated anti-cancer target. The HaloTag ligand moiety binds covalently to HaloTag protein (an engineered dehalogenase), allowing the conjugate to be selectively anchored to HaloTag-fused proteins (e.g., mutant p53). This restricts PLK1 inhibition to HaloTag-expressing cells, providing a proof-of-concept for targeted therapy.
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| ln Vitro |
In vitro, BI2536-PEG2-Halo inhibits the proliferation of 293T cells expressing Halo-p53R273H(FL)-mCherry (p53 mutant) with an IC₅0 of 23 nM. Cells not expressing the HaloTag show much lower sensitivity (IC₅0 > 1 uM), demonstrating selective toxicity against p53-mutant cancer cells expressing the HaloTag. The compound inhibits PLK1 activity (as measured by reduced phosphorylation of PLK1 substrates such as Cdc25C and MYPT1) in HaloTag-expressing cells. The PEG2 linker provides flexibility and solubility. The compound is a research tool for validating molecular glue or targeted degradation strategies; it demonstrates that PLK1 inhibition can be selectively delivered to mutant p53-expressing cells via HaloTag conjugation.
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| ln Vivo |
In vivo activity has not been reported; the compound is intended for cellular proof-of-concept studies. In principle, if a HaloTag-fused protein is expressed in tumors in vivo (e.g., via viral delivery or transgenic mouse), BI2536-PEG2-Halo could be used to achieve selective PLK1 inhibition in those tumors. However, this is not yet demonstrated.
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| Enzyme Assay |
For cellular assays, 293T cells are transiently transfected with a construct encoding Halo-p53R273H(FL)-mCherry fusion protein. After 24-48 hours, cells are seeded in 96-well plates (5,000-10,000 cells/well) and treated with BI2536-PEG2-Halo (0.1 nM-10 uM) or vehicle (DMSO ≤0.1%) for 48-72 hours. Cell viability is assessed by MTT or CellTiter-Glo. IC₅0 values are calculated. For PLK1 activity, cells are treated with 50-500 nM compound for 4-24 hours, lysed in RIPA buffer, and Western blotted for p-Cdc25C (Ser216), p-MYPT1 (Thr696), and total PLK1. For apoptosis detection, Annexin V/PI staining and flow cytometry are performed. For HaloTag labeling, cells are incubated with a fluorescent HaloTag ligand (e.g., HaloTag TMR Ligand, 1-5 uM) for 30 minutes, fixed, and imaged by fluorescence microscopy to confirm HaloTag expression. For selectivity validation, control cells not expressing HaloTag are treated in parallel.
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| Cell Assay |
Not applicable.
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| ADME/Pharmacokinetics |
The compound is supplied as a powder soluble in DMSO (100 mg/mL). For in vitro use, prepare a 10 mM stock in DMSO. It is stable for 3 years at -20degC as powder, 6 months at -80degC in solution. No in vivo PK data are available.
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| Toxicity/Toxicokinetics |
No toxicity data beyond cellular IC₅0. At 23 nM, the compound is non-toxic to cells lacking the HaloTag. Standard laboratory safety precautions: wear gloves, goggles, lab coat. Not for human use.
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| References | |
| Additional Infomation |
BI2536-PEG2-Halo is a chemical probe for targeted PLK1 inhibition via HaloTag anchoring. It is a research tool, not an approved drug. For research use only.
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| Molecular Formula |
C39H60CLN7O8
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| Molecular Weight |
790.39
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| Appearance |
White to off-white oil
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2652 mL | 6.3260 mL | 12.6520 mL | |
| 5 mM | 0.2530 mL | 1.2652 mL | 2.5304 mL | |
| 10 mM | 0.1265 mL | 0.6326 mL | 1.2652 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
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