| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
CDK5 0.95 μM (IC50) CDK1 1.1 μM (IC50) CLK1 DYRK1A GSK-3
(R)-(+)-O-Demethylbuchenavianine targets cyclin-dependent kinases (CDKs), specifically CDK1 and CDK5. CDK1 is a master regulator of the cell cycle, controlling G2/M transition. CDK5 is primarily active in post-mitotic neurons, regulating neuronal migration, synaptic plasticity, and cytoskeletal dynamics. The compound inhibits CDK1 with an IC50 of 1.1 microM and CDK5 with an IC50 of 0.95 microM. It also shows weak inhibitory activity against glycogen synthase kinase 3 (GSK3), cdc2-like kinase (CLK1), and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) with IC50 values >10 microM. This selectivity suggests it may be useful for studying CDK5-related neurological pathways. |
|---|---|
| ln Vitro |
In vitro, (R)-(+)-O-Demethylbuchenavianine inhibits CDK1 and CDK5 kinase activity with IC50 values of 1.1 microM and 0.95 microM, respectively. It demonstrates selectivity for these CDKs over GSK3, CLK1, and DYRK1A (IC50 >10 microM for each). No specific cellular activity data (e.g., cell cycle arrest in CDK1-dependent cancer cells, neurite outgrowth in CDK5-inhibited neurons) are reported in the search results. The compound is a tool for studying the role of CDK1 in cell cycle regulation and CDK5 in neuronal function and neurodegeneration. No IC50 values for CDK2, CDK4, or CDK6 are reported. It may inhibit other kinases as well; a broader kinase panel would be needed.
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| ln Vivo |
No in vivo activity data for (R)-(+)-O-Demethylbuchenavianine are reported in the search results. As a CDK1 and CDK5 inhibitor, it could potentially be evaluated in vivo in cancer models (CDK1 inhibition leads to G2/M arrest and apoptosis) or in neurological disease models (CDK5 dysregulation is implicated in Alzheimer‘s disease, Parkinson's disease, and amyotrophic lateral sclerosis). The compound could be used in mouse xenograft models of CDK1-dependent cancers (e.g., certain breast, ovarian, or colorectal cancers) or in transgenic mouse models of tauopathy (CDK5 phosphorylates tau, contributing to neurofibrillary tangle formation). However, no such in vivo data are provided in the search results.
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| Enzyme Assay |
Binding affinity to CDK1 and CDK5 is measured by standard in vitro kinase assays using purified recombinant human CDK1/cyclin B or CDK5/p25 (or p35) complexes. The compound is incubated with the kinase, a substrate (e.g., histone H1 for CDK1, or a peptide substrate for CDK5), and ATP (including gamma-32P-ATP for radiometric assays or using non-radioactive ADP-Glo™ assays). After incubation, the incorporated radioactivity is measured by scintillation counting, or ADP production is measured by luminescence. IC50 values (1.1 microM for CDK1, 0.95 microM for CDK5) are calculated from dose-response curves (0.001-100 microM). Selectivity against GSK3, CLK1, DYRK1A is confirmed by parallel assays using their respective recombinant enzymes and specific substrates.
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| Cell Assay |
No cellular assays for (R)-(+)-O-Demethylbuchenavianine are described in the search results. For cellular CDK inhibition studies, cancer cell lines (e.g., HeLa, MCF-7, A549, HCT116) would be seeded in 6- or 96-well plates and treated with (R)-(+)-O-Demethylbuchenavianine at graded concentrations (0.1-100 microM) for 24-72 h. Cell cycle analysis would be performed by propidium iodide staining and flow cytometry to measure G2/M arrest (a hallmark of CDK1 inhibition). Cell viability would be assessed by MTT or CellTiter-Glo to calculate IC50 values. For CDK5-specific assays, neuronal cell lines (e.g., SH-SY5Y, Neuro2a, or primary cortical neurons) would be treated with the compound, and tau phosphorylation at CDK5-specific sites (e.g., Ser202, Thr205, Ser396, Ser404) would be assessed by Western blot with phospho-specific antibodies (e.g., AT8, PHF1, pSer396). No such data are reported.
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| Animal Protocol |
No animal experiments for (R)-(+)-O-Demethylbuchenavianine are described in the search results. For in vivo evaluation of CDK1 inhibition, 6-8-week-old female BALB/c nude mice bearing subcutaneous tumor xenografts of CDK1-dependent cancer cell lines would be treated orally or intraperitoneally with the compound at doses of 10-100 mg/kg daily for 2-4 weeks. Tumor volumes would be measured, and tumors would be analyzed for cell cycle arrest (by flow cytometry) and apoptosis (by caspase-3 activation). For CDK5-related neurological studies, transgenic tauopathy mice (e.g., P301S, rTg4510) or Alzheimer‘s disease model mice could be treated with the compound, and tau phosphorylation, neuroinflammation, and cognitive function (Morris water maze) would be assessed. No such data are provided.
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| ADME/Pharmacokinetics |
(R)-(+)-O-Demethylbuchenavianine (C21H21NO4, MW = 351.40) is a solid powder. For storage, the compound should be kept at -20degC sealed, away from moisture and light. For in vitro use, stock solutions in DMSO (10-50 mM) can be stored at -80degC for up to 6 months or at -20degC for 1 month. Solubility in water is likely low due to the lipophilic flavonoid structure. For in vivo use, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween-80 / 45% saline or 0.5% methylcellulose/0.1% Tween-80. Purity is ≥98% (HPLC). No detailed PK parameters (oral bioavailability, Cmax, Tmax, half-life, brain penetration) are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for (R)-(+)-O-Demethylbuchenavianine are reported in the search results. As a research-grade compound, it is not intended for human use. Standard laboratory safety precautions for handling kinase inhibitors should be followed. Based on its inhibition of CDK1 (a cell cycle regulator essential for normal cell division), systemic inhibition of CDK1 could cause significant toxicity, including myelosuppression, gastrointestinal toxicity, and alopecia, similar to other CDK1 inhibitors. However, no such toxicity studies have been reported. No LD50 or formal toxicology data are available.
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| References | |
| Additional Infomation |
(R)-(+)-O-Demethylbuchenavianine is a research-grade natural product derivative (chiral flavonoid alkaloid) isolated or synthesized as a tool for studying cyclin-dependent kinases. It is characterized by a 5,7-dihydroxyflavone core linked to a 1-methylpiperidin-2-yl moiety at C-8. The compound is the O-demethylated derivative of buchenavianine, an alkaloid found in some plant species (likely Buchenavia species). It shows selectivity for CDK1 and CDK5 (IC50 ~1 microM) over GSK3, CLK1, and DYRK1A (>10 microM). CDK5 is an attractive target for Alzheimer‘s disease because CDK5 hyperactivation leads to tau hyperphosphorylation, neurofibrillary tangle formation, and neurodegeneration. This compound could serve as a lead for developing more potent and selective CDK5 inhibitors for Alzheimer's disease and other tauopathies. The compound is for research use only and has not entered clinical trials or received regulatory approval.
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| Molecular Formula |
C21H21NO4
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|---|---|
| Molecular Weight |
351.40
|
| Exact Mass |
351.147
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| CAS # |
1364123-68-1
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| PubChem CID |
57342709
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
2
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
26
|
| Complexity |
556
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1CCCC[C@@H]1C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4)O)O
|
| InChi Key |
BBZGOLNDVQZCIH-CQSZACIVSA-N
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| InChi Code |
InChI=1S/C21H21NO4/c1-22-10-6-5-9-14(22)19-15(23)11-16(24)20-17(25)12-18(26-21(19)20)13-7-3-2-4-8-13/h2-4,7-8,11-12,14,23-24H,5-6,9-10H2,1H3/t14-/m1/s1
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| Chemical Name |
5,7-dihydroxy-8-[(2R)-1-methylpiperidin-2-yl]-2-phenylchromen-4-one
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 2.8458 mL | 14.2288 mL | 28.4576 mL | |
| 5 mM | 0.5692 mL | 2.8458 mL | 5.6915 mL | |
| 10 mM | 0.2846 mL | 1.4229 mL | 2.8458 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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