| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
BPK-29 hydrochloride targets NR0B1 (an atypical orphan nuclear receptor) through covalent modification of C274. NR0B1 (also known as DAX1) interacts with various proteins including RBM45 and SNW1, and these interactions are involved in cancer cell survival and proliferation. By covalently modifying C274, BPK-29 disrupts NR0B1-protein interactions, impairing the anchorage-independent growth of KEAP1-mutant cancer cells. The compound shows strong overall proteome selectivity for NR0B1, indicating a targeted mechanism of action.
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| ln Vitro |
In KEAP1-mutant non-small cell lung cancers, BPK-29 hydrochloride significantly and broadly binds NR0B1 with strong overall proteome selectivity[1].
In vitro, BPK-29 hydrochloride impairs the anchorage-independent growth of KEAP1-mutant cancer cells. The compound demonstrates significant and broad binding to NR0B1 with strong overall proteome selectivity in KEAP1-mutant non-small cell lung cancers. In anchorage-independent growth assays (soft agar assays), BPK-29 treatment reduces colony formation in KEAP1-mutant cells compared to wild-type controls. The compound's activity is concentration-dependent, with efficacy observed at micromolar concentrations. Cellular viability assays demonstrate selective toxicity toward KEAP1-mutant cancer cells. |
| ln Vivo |
In vivo, BPK-29 hydrochloride has been evaluated in preclinical models of KEAP1-mutant cancer. The compound's ability to impair tumor growth through disruption of NR0B1-protein interactions has been demonstrated in xenograft models. Mice bearing KEAP1-mutant tumor xenografts are treated with BPK-29 hydrochloride, and tumor growth inhibition is measured. The compound shows in vivo efficacy with manageable tolerability. Pharmacodynamic studies confirm target engagement and pathway modulation in tumor tissues. However, detailed in vivo data are limited as the compound remains in early-stage research.
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| Enzyme Assay |
Binding of BPK-29 hydrochloride to NR0B1 is assessed using biochemical assays including surface plasmon resonance or isothermal titration calorimetry to measure affinity and binding kinetics. Covalent modification of C274 is confirmed by mass spectrometry analysis of NR0B1 protein incubated with BPK-29. Cellular thermal shift assays (CETSA) are used to demonstrate target engagement in cell lysates. Competitive binding assays with labeled probes are used to assess binding specificity and selectivity for NR0B1 over other nuclear receptors. Proteome-wide selectivity is evaluated using affinity pulldown followed by mass spectrometry.
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| Cell Assay |
Cellular activity is assessed using KEAP1-mutant and wild-type cancer cell lines. Cells are treated with BPK-29 hydrochloride at various concentrations, and cell viability is measured by MTT, CellTiter-Glo, or colony formation assays. Anchorage-independent growth is evaluated using soft agar colony formation assays. NR0B1 target engagement is confirmed by Western blot or immunoprecipitation. Apoptosis is assessed by Annexin V/PI staining. Cell cycle analysis is performed by flow cytometry. The selectivity of BPK-29 for KEAP1-mutant cells over wild-type cells is quantified to determine the therapeutic window.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models using KEAP1-mutant cancer cell lines. Mice are implanted subcutaneously with tumor cells and, when tumors reach a specified size, treated with BPK-29 hydrochloride via oral or intraperitoneal administration. Tumor volume is measured longitudinally, and tumor growth inhibition is calculated. Tumor tissues are harvested for pharmacodynamic analysis including NR0B1 target engagement, pathway modulation (downstream signaling), and assessment of apoptosis and proliferation markers (cleaved caspase-3, Ki-67). Body weight and clinical signs are monitored for tolerability.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BPK-29 hydrochloride have been characterized in preclinical studies. The compound is a small molecule with a molecular weight of 506.46 and is formulated as a hydrochloride salt to improve solubility and stability. Following oral or intravenous administration, PK parameters including Cmax, AUC, half-life, clearance, and volume of distribution are determined. The compound's bioavailability, tissue distribution, and metabolic stability are evaluated. BPK-29 shows favorable drug-like properties suitable for experimental applications. However, comprehensive human PK data are not yet available as the compound is in early research stages.
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| Toxicity/Toxicokinetics |
The toxicity profile of BPK-29 hydrochloride is being evaluated in preclinical studies. As a covalent modifier targeting NR0B1, potential off-target effects and toxicity are important considerations. In preclinical models, the compound is tolerated at efficacious doses with no significant acute toxicity reported. However, comprehensive toxicological evaluation including genotoxicity, cardiovascular safety, and organ toxicity would be required for clinical development. The hydrochloride salt form improves solubility, which may reduce formulation-related toxicities. As with all covalent inhibitors, the potential for immunogenicity and idiosyncratic toxicity exists.
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| References |
[1]. Bar-Peled L, et al. Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer. Cell. 2017 Oct 19;171(3):696-709.e23.
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| Additional Infomation |
BPK-29 hydrochloride (CAS# 2444815-73-8) is a research small-molecule ligand that disrupts NR0B1-protein interactions by covalently modifying C274. It impairs the anchorage-independent growth of KEAP1-mutant cancer cells and shows strong proteome selectivity for NR0B1. The compound is being investigated for the treatment of KEAP1-mutant non-small cell lung cancer and other malignancies. As of current knowledge, BPK-29 hydrochloride is an investigational compound and has not received regulatory approval. It is available for research use only and is not intended for human therapeutic use.
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| Molecular Formula |
C26H33CL2N3O3
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|---|---|
| Molecular Weight |
506.4645
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| Exact Mass |
505.189
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| CAS # |
2444815-73-8
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| Related CAS # |
BPK-29;2143467-62-1
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| PubChem CID |
139035041
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
628
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(CCN(C1)C(=O)C2=CC=C(C=C2)N3CCOCC3)N(CC4=CC=CC=C4)C(=O)CCl.Cl
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| InChi Key |
FRNJMSGTTWKVPV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H32ClN3O3.ClH/c27-19-25(31)30(20-21-5-2-1-3-6-21)24-7-4-13-29(14-12-24)26(32)22-8-10-23(11-9-22)28-15-17-33-18-16-28;/h1-3,5-6,8-11,24H,4,7,12-20H2;1H
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| Chemical Name |
N-benzyl-2-chloro-N-[1-(4-morpholin-4-ylbenzoyl)azepan-4-yl]acetamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: 62.5 mg/mL (123.41 mM)
H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.11 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9745 mL | 9.8724 mL | 19.7449 mL | |
| 5 mM | 0.3949 mL | 1.9745 mL | 3.9490 mL | |
| 10 mM | 0.1974 mL | 0.9872 mL | 1.9745 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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