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| 1mg |
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| Targets |
The primary targets of BMS-986463 are the E3 ubiquitin ligase CRBN (Cereblon) and the WEE1 kinase. As a CELMoD, it binds to CRBN, altering its substrate specificity. This results in the ubiquitination and subsequent proteasomal degradation of WEE1, a protein essential for the G2/M cell cycle checkpoint. By degrading WEE1, the compound abrogates the DNA damage checkpoint, leading to premature mitotic entry and cell death in cancer cells. It significantly inhibits tumor regression and reduces phosphorylated CDK2 (p‑CDK2) levels, a downstream marker of WEE1 activity.
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| ln Vitro |
WEE1 tyrosine kinase is an important cell cycle regulator. Its main function is to inhibit cell cycle progression in the S phase and G2/M phase, thereby preventing DNA-damaged cells from mitotically dividing [1].
In vitro, BMS-986463 is a CRBN E3 ligase modulator (CELMoD) and a WEE1 kinase molecular glue degrader. It leads to the degradation of the WEE1 protein. This results in the reduction of phosphorylated CDK2 (p‑CDK2) levels, a key substrate of WEE1. The degradation of WEE1 induces cell cycle progression in the presence of DNA damage, leading to mitotic catastrophe and cell death. It can be used in research of advanced malignant solid tumors like non‑small cell lung cancer (NSCLC). |
| ln Vivo |
In vivo, BMS-986463 significantly inhibits tumor regression in animal models. It reduces phosphorylated CDK2 levels in tumor tissue, confirming target engagement. It is used in the research of advanced malignant solid tumors such as non‑small cell lung cancer (NSCLC). It has been studied in advanced cancer, ovarian high‑grade serous adenocarcinoma, and non‑small cell lung cancer.
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| Enzyme Assay |
Non-cell-based (cell-free) experiments for BMS-986463 are not typical, as its mechanism requires the cellular ubiquitin‑proteasome system. However, the binding affinity to CRBN can be studied in a cell-free system. Recombinant CRBN protein is incubated with BMS-986463 in a buffer, and the binding affinity (KD) is measured by surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The ability of the compound to promote the formation of a ternary complex (CRBN‑compound‑WEE1) can be assessed by an AlphaLISA or homogeneous time-resolved fluorescence (HTRF) assay using labeled CRBN and WEE1 proteins.
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| Cell Assay |
Cell-based assays for BMS-986463 are conducted in NSCLC cell lines (e.g., NCI‑H1299, A549). Cells are seeded in 6‑well or 96‑well plates and treated with increasing concentrations of the compound (0.1-1000 nM) for 24-72 hours. After treatment, cells are lysed, and the levels of WEE1, phosphorylated CDK2 (p‑CDK2), and other cell cycle markers are measured by Western blotting. Cell viability is measured by CellTiter‑Glo or MTT assay. The IC₅0 for growth inhibition is calculated. The effect on the cell cycle is analyzed by flow cytometry with propidium iodide (PI) staining to measure the accumulation of cells in the G2/M phase. Apoptosis is assessed by Annexin V/PI staining.
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| Animal Protocol |
In vivo animal experiments for BMS-986463 are conducted in mouse xenograft models of NSCLC. Nude mice are implanted subcutaneously with NSCLC cells (e.g., NCI‑H1299). When tumors reach a certain size (e.g., 100-200 mm3), mice are randomized to treatment groups. BMS-986463 is administered orally or intravenously at doses of 0.1-10 mg/kg daily or every other day for 2-4 weeks. Tumor volume is measured by calipers twice weekly. At the endpoint, tumors are collected and analyzed for WEE1 and p‑CDK2 levels by Western blotting and immunohistochemistry (IHC). The compound significantly inhibits tumor regression and reduces phosphorylated CDK2 levels.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for BMS-986463 are not available in the provided material. The compound has a molecular weight of 572.63 g/mol. It has a CAS number of 3025467-07-3 and is stored at -20degC. The product is for research use only and not for human use. The stability of solutions is poor; solutions are unstable, so it must be prepared fresh or purchased in small, pre-packaged sizes.
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| Toxicity/Toxicokinetics |
The toxicity of BMS-986463 has not been fully characterized. As a research chemical that degrades an essential cell cycle protein, it has the potential to cause significant cytotoxicity. Standard safety precautions apply: the compound may be harmful if swallowed, inhaled, or absorbed through the skin. It may cause skin and eye irritation. It should be handled in a well-ventilated area (fume hood) with appropriate PPE (lab coat, gloves, safety goggles). The product is not for human or veterinary use.
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| References | |
| Additional Infomation |
Additional information: The compound has a CAS number of 3025467-07-3. It is also known as WEE1 CELMoD, BMS‑986463, and BMS‑986463. It is a novel, first‑in‑class targeted protein degrader designed to specifically eliminate WEE1 kinase. It is available as a research tool for protein degradation studies and cancer research.
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| Molecular Formula |
C32H33FN4O5
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| Molecular Weight |
572.63
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| CAS # |
3025467-07-3
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| Appearance |
White to off-white solid powder
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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) |
DMSO : ~2 mg/mL (~3.49 mM; with sonication (<60°C))
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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 | 1.7463 mL | 8.7316 mL | 17.4633 mL | |
| 5 mM | 0.3493 mL | 1.7463 mL | 3.4927 mL | |
| 10 mM | 0.1746 mL | 0.8732 mL | 1.7463 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.
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