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| Targets |
BPK-25 has multiple reported targets: (1) The NuRD complex, a multi-protein chromatin remodeling complex (including CHD3/4, HDAC1/2, MTA1/2/3, MBD2/3). BPK-25 promotes the degradation of NuRD complex proteins. (2) It inhibits TMEM173 (STING) activation by the cyclic dinucleotide ligand cGAMP, thereby suppressing NF-kappaB activation. It also has been reported to inhibit CDK9.
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| ln Vitro |
TMEM173 activation is inhibited by BPK-25 (10 μM; 5 hours) through the cyclic dinucleotide ligand cGAMP [2]. As indicated by a >50% decrease in IκBα phosphorylation, BPK-25 (10 μM; 24 hours) suppresses nuclear factor of activated T cells (NFAT) activation and NF-κB activation [1]. T cell NFATc2 expression is likewise decreased by BPK-25 (10 μM; 4 hours) [1]. In a concentration- and time-dependent manner, BPK-25 (0.1, 1, 5, 10, 20 μM; 24 hours) promotes the substantial and selective decrease of many proteins in the nucleosome remodeling and deacetylation (NuRD) complex. The mRNA expression of BPK-25 did not alter in a similar way [1]. BPK-25-ctrl, the non-electrophilic propionamide analog of BPK-25, does not change NuRD complex proteins in T cells or limit T cell activation [1].
In vitro, BPK-25 inhibits TMEM173 activation by the cyclic dinucleotide ligand cGAMP, which in turn inhibits the activation of NF-kappaB. It also promotes the degradation of nucleosome remodeling and deacetylation (NuRD) complex proteins. At low uM concentrations, it has been reported to suppress T-cell activation without causing cytotoxicity. The compound is an active acrylamide, suggesting it may act as a covalent inhibitor, leading to the degradation of its target proteins. |
| ln Vivo |
In vivo, BPK-25 has been reported as a tool to study NuRD complex biology and immune modulation. By promoting NuRD complex degradation, it can affect T-cell function and chromatin remodeling. It has been noted to suppress T-cell activation at low micromolar concentrations, indicating potential immunosuppressive activity. However, detailed in vivo efficacy data from animal models is not provided in standard literature, and its primary use is as a research tool for target validation.
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| Enzyme Assay |
There is no standard cell-free assay for BPK-25 due to its mechanism as a degrader (likely via a proteasomal pathway). Researchers might use an in vitro ubiquitination assay to see if BPK-25 enhances the ubiquitination of NuRD complex components, but this is not a routine protocol. Binding assays such as Surface Plasmon Resonance could be used to confirm direct binding to a target protein, but the main activity (degradation) is measured in cells.
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| Cell Assay |
A standard cellular assay for BPK-25 is to assess its effect on NuRD complex proteins and T-cell activation. Jurkat T cells or primary human T cells are treated with BPK-25. After 24-48 hours, cells are collected, lysed, and the levels of NuRD complex proteins (e.g., CHD4, HDAC1/2) are analyzed by Western blotting to confirm degradation. T-cell activation is induced by anti-CD3/CD28 antibodies, and activation markers (e.g., CD25, CD69) are measured by flow cytometry, and cytokine production (e.g., IL-2, IFN-gamma) is measured by ELISA. Inhibition of TMEM173 activation can be assessed in reporter cell lines expressing STING.
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| Animal Protocol |
For in vivo studies, animal models (typically mice) are used to study T-cell mediated immune disorders. Mice are administered BPK-25 via intraperitoneal (IP) injection or oral gavage. A model of graft-versus-host disease (GvHD) or a T-cell mediated inflammatory disease model could be used. Endpoints include T-cell activation markers in the spleen and lymph nodes, cytokine levels in serum, and histopathological assessment of target organs (e.g., colon, liver, skin). Specific dosing regimens are not detailed in standard literature.
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| ADME/Pharmacokinetics |
BPK-25 has a molecular weight of 392.84 and a molecular formula of C21H17ClN4O2. It is an active acrylamide, which can be reactive. It has high solubility in DMSO (150 mg/mL). For in vivo use, it would be formulated in vehicles such as DMSO:PEG300:Tween80:Saline to ensure solubility and stability. Specific pharmacokinetic parameters (e.g., half-life, bioavailability) are not detailed in standard sources. The presence of the acrylamide warhead suggests it is a covalent inhibitor, which can impact the duration of its pharmacodynamic effect.
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| Toxicity/Toxicokinetics |
Specific toxicological data for BPK-25 is not available in the reference literature. As an active acrylamide, this compound has the potential for off-target reactivity with cellular proteins containing cysteine residues, which is the basis for its mechanism of action but could also lead to non-specific toxicity. It was designed to be selective, suppressing T-cell activation without causing cytotoxicity in vitro, but a full toxicological profile is not available. It should be handled as a potentially hazardous chemical.
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| References |
[1]. Ekaterina V Vinogradova, et al. An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29.
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| Additional Infomation |
BPK-25 is a research chemical tool for studying the NuRD (Nucleosome Remodeling and Deacetylation) complex, which is a multi-subunit complex that plays a critical role in transcriptional regulation, development, and cancer. It is also used to study the cGAS-STING pathway and CDK9 biology. The compound is a degrader, which is an emerging strategy for drug discovery. By promoting the degradation of its target proteins, it has a different pharmacological profile than a traditional inhibitor. BPK-25 is not an approved drug and is strictly for preclinical research. There are contradictory reports in the search results (some describe it as a CDK9 inhibitor, others as a NuRD degrader and STING inhibitor), suggesting it may have multiple activities or that the literature is ambiguous.
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| Molecular Formula |
C21H17CLN4O2
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| Molecular Weight |
392.84
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| Exact Mass |
392.104
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| CAS # |
2305052-86-0
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| PubChem CID |
138506238
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.4
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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 |
28
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| Complexity |
553
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C=CC(=O)N(CC1=NC(=CC=C1)Cl)C2=CN=C(C=C2)C(=O)NC3=CC=CC=C3
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| InChi Key |
MHPBTJANPDDCPH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H17ClN4O2/c1-2-20(27)26(14-16-9-6-10-19(22)24-16)17-11-12-18(23-13-17)21(28)25-15-7-4-3-5-8-15/h2-13H,1,14H2,(H,25,28)
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| Chemical Name |
5-[(6-chloropyridin-2-yl)methyl-prop-2-enoylamino]-N-phenylpyridine-2-carboxamide
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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 (e.g. under nitrogen), 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: 150 mg/mL (381.83 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 3.75 mg/mL (9.55 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 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: ≥ 3.75 mg/mL (9.55 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 37.5 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: ≥ 3.75 mg/mL (9.55 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 | 2.5456 mL | 12.7278 mL | 25.4557 mL | |
| 5 mM | 0.5091 mL | 2.5456 mL | 5.0911 mL | |
| 10 mM | 0.2546 mL | 1.2728 mL | 2.5456 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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