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| Targets |
BPKDi targets protein kinase D (PKD), a family of serine/threonine kinases that includes three isoforms: PKD1, PKD2, and PKD3. PKD is involved in diverse cellular processes including signal transduction, gene expression, vesicular trafficking, and cardiac hypertrophy. BPKDi inhibits PKD1, PKD2, and PKD3 with IC50 values of 1 nM, 9 nM, and 1 nM, respectively. It is selective for PKD over PKCδ and PKCε, as well as over a panel of additional calcium/calmodulin-dependent protein kinase (CaMK) superfamily members, at 1 µM. By inhibiting PKD, BPKDi blocks the phosphorylation and nuclear export of class IIa HDACs, which are key regulators of gene expression in response to stress signals. This mechanism makes BPKDi a valuable tool for studying PKD-mediated signaling pathways in various biological contexts.
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| ln Vitro |
In vitro studies have demonstrated that BPKDi is a highly potent inhibitor of PKD isoforms. It inhibits PKD1, PKD2, and PKD3 with IC50 values of 1 nM, 9 nM, and 1 nM, respectively. The compound shows selectivity for PKD over related kinases such as PKCδ and PKCε, as well as over a panel of additional CaMK superfamily members, at 1 µM. In cellular assays using isolated neonatal rat ventricular myocytes, BPKDi at a concentration of 1 µM inhibits phenylephrine-induced phosphorylation and nuclear export of histone deacetylase 4 (HDAC4) and HDAC5. It also reduces phenylephrine-induced hypertrophy in these cells. These findings confirm that BPKDi is a potent and selective inhibitor of PKD with functional activity in cardiac cells.
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| ln Vivo |
In vivo activity data for BPKDi is limited, as the compound is primarily used as a research tool in in vitro studies. However, its mechanism of action—inhibiting PKD-mediated phosphorylation and nuclear export of class IIa HDACs—suggests potential in vivo applications in studying cardiac hypertrophy and other PKD-related pathologies. The compound's selectivity for PKD over other kinases makes it a suitable candidate for in vivo studies to validate PKD as a therapeutic target. However, specific in vivo protocols and results, such as dosing regimens, routes of administration, and pharmacokinetic parameters, are not detailed in the available literature. BPKDi is primarily used for in vitro research to dissect PKD signaling pathways.
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| Enzyme Assay |
The in vitro enzyme assays for BPKDi measure its inhibition of PKD kinase activity. In a typical assay, recombinant PKD isoforms (PKD1, PKD2, or PKD3) are incubated with a peptide substrate and ATP in the presence of varying concentrations of BPKDi. The incorporation of phosphate into the substrate is measured using a radiometric (e.g., 33P-ATP) or fluorescent method. The inhibition of kinase activity is calculated, and the IC50 is determined from the dose-response curve. For BPKDi, the IC50 values for PKD1, PKD2, and PKD3 are 1 nM, 9 nM, and 1 nM, respectively. To confirm selectivity, the compound is tested against a panel of other kinases, including PKCδ, PKCε, and CaMK superfamily members. These assays provide a quantitative measure of BPKDi's potency and selectivity at the molecular level.
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| Cell Assay |
In vitro cell-based assays for BPKDi are used to study its effects on PKD-mediated signaling in a cellular context. A common model is the use of isolated neonatal rat ventricular myocytes. In these assays, cells are treated with phenylephrine to induce hypertrophy and PKD activation. BPKDi is added at concentrations such as 1 µM, and its effects on phosphorylation and nuclear export of HDAC4 and HDAC5 are assessed by Western blotting and immunofluorescence. The compound's ability to reduce phenylephrine-induced hypertrophy is measured by assessing cell size or protein synthesis. These cell-based assays confirm that BPKDi inhibits PKD activity and downstream signaling in a physiologically relevant cellular model.
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| Animal Protocol |
In vivo animal experiments for BPKDi are not extensively described in the available literature. As a research compound, its use in vivo would be determined by the specific research question being addressed. A typical protocol for studying a PKD inhibitor like BPKDi would involve its administration to animal models of cardiac hypertrophy or other PKD-related diseases. The compound would be formulated for injection, likely using a vehicle that includes DMSO, PEG, and saline. It could be administered via intraperitoneal (i.p.) or intravenous (i.v.) injection at a predetermined dose and schedule. Endpoints would include assessment of cardiac function, hypertrophy markers, and HDAC phosphorylation. However, specific protocols for BPKDi are not detailed in the available literature.
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| ADME/Pharmacokinetics |
BPKDi has a molecular weight of 380.49 g/mol and a molecular formula of C21H28N6O. It has a logP of 2.2. The compound is soluble in DMSO. For storage, it is recommended to keep the powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. The compound should be stored in a sealed and protected environment (e.g., under nitrogen), avoiding exposure to moisture and light. It is stable at ambient temperature for a few days during shipping. Detailed pharmacokinetic properties such as half-life, bioavailability, and tissue distribution have not been extensively characterized.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for BPKDi is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. In vitro studies have shown that the compound is selective for PKD over other kinases, suggesting that it may have a favorable off-target safety profile. However, comprehensive toxicological studies, including acute and chronic toxicity studies, have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling BPKDi. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References | |
| Additional Infomation |
BPKDi is a research compound and is not approved for any clinical or therapeutic use. It is a potent and selective inhibitor of protein kinase D (PKD), with IC50 values of 1 nM, 9 nM, and 1 nM for PKD1, PKD2, and PKD3, respectively. BPKDi blocks signal-dependent phosphorylation and nuclear export of class IIa HDACs in cardiomyocytes. It is used as a research tool to study the role of PKD in cellular processes such as cardiac hypertrophy, gene expression, and vesicular trafficking. The compound's mechanism of action involves inhibiting PKD kinase activity, thereby preventing the phosphorylation and nuclear export of class IIa HDACs. BPKDi is a valuable tool for dissecting PKD-mediated signaling pathways and for validating PKD as a therapeutic target for diseases such as cardiac hypertrophy and cancer.
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| Molecular Formula |
C21H28N6O
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| Molecular Weight |
380.486623764038
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| Exact Mass |
380.232
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| CAS # |
1201673-28-0
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| PubChem CID |
46901383
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
505
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=C(C2C=CN=C(C=2)NC2CCCCC2)N=C(C=1)N1CCNCC1)N
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| InChi Key |
XNWDRALEEPGBHB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H28N6O/c22-21(28)16-12-18(26-20(14-16)27-10-8-23-9-11-27)15-6-7-24-19(13-15)25-17-4-2-1-3-5-17/h6-7,12-14,17,23H,1-5,8-11H2,(H2,22,28)(H,24,25)
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| Chemical Name |
2-[2-(cyclohexylamino)pyridin-4-yl]-6-piperazin-1-ylpyridine-4-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 and light. |
| 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 | 2.6282 mL | 13.1409 mL | 26.2819 mL | |
| 5 mM | 0.5256 mL | 2.6282 mL | 5.2564 mL | |
| 10 mM | 0.2628 mL | 1.3141 mL | 2.6282 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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