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| Targets |
CDK4 and CDK6 (cyclin-dependent kinases 4 and 6). Tanuxiciclib selectively binds to and inhibits CDK4 and CDK6, key regulators of the G1 to S phase cell cycle transition. By blocking the phosphorylation of the retinoblastoma (Rb) protein, Tanuxiciclib prevents the release of E2F transcription factors, leading to sustained G1 arrest in Rb-proficient cancer cells. This inhibition suppresses the proliferation of cancer cells, particularly in hormone receptor-positive breast cancer.
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| ln Vitro |
Tanuxiciclib is a potent and selective CDK4/6 inhibitor. While specific IC50 values are not provided in the search results, it is expected to have activity in the low nanomolar range. It is used in cancer research to study the effects of CDK4/6 inhibition on cell cycle progression and tumor cell proliferation. It is an active comparator in research studies.
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| ln Vivo |
Tanuxiciclib trihydrochloride (BPI-1178) has a maximum clinical trial phase of Phase I, indicating that it has been tested in humans for safety and preliminary efficacy. It is being studied for the treatment of various cancers, including breast cancer. In vivo efficacy would have been demonstrated in preclinical xenograft models, showing tumor growth inhibition. Phase I trials are designed to determine maximum tolerated dose, safety, and pharmacokinetics.
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| Enzyme Assay |
Tanuxiciclib is a CDK4/6 inhibitor. For a cell-free enzymatic assay, purified CDK4/cyclin D1 or CDK6/cyclin D1 complexes are incubated with varying concentrations of Tanuxiciclib (0.1 nM-100 uM) in a reaction buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT) for 15-30 minutes at room temperature. The reaction is initiated by adding a retinoblastoma (Rb) peptide substrate (1 uM) and ATP (10-100 uM, with 33P-ATP or a fluorescent label). After 60 minutes at 30degC, the reaction is quenched with EDTA, and the amount of phosphorylated Rb peptide is quantified by filter binding or FRET. IC50 values are calculated.
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| Cell Assay |
For in vitro cellular studies, Rb-proficient breast cancer cell lines (e.g., MCF-7, T47D) are seeded in 96-well plates (5×103 cells/well) and treated with Tanuxiciclib at concentrations ranging from 0.1 nM-10 uM for 48-96 hours. Cell viability is measured using the CellTiter-Glo (ATP) assay. To confirm CDK4/6 inhibition, cells are treated for 24-48 hours, and the phosphorylation of Rb (at Ser780 or Ser795) is measured by Western blotting. Cell cycle analysis is performed by flow cytometry after propidium iodide (PI) staining, where an increase in the percentage of cells in G1 phase is expected. Apoptosis is assessed by measuring caspase 3/7 activity. The effect of the compound on cell proliferation can also be assessed by Ki67 staining by flow cytometry or immunofluorescence.
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| Animal Protocol |
A typical in vivo protocol for a CDK4/6 inhibitor involves establishing subcutaneous xenografts of a breast cancer cell line (e.g., MCF-7, T47D, or a patient-derived xenograft model) in 6-8 week old female BALB/c nude mice. When tumors reach ~150-200 mm3, mice are randomized into treatment groups (n=8-10). Tanuxiciclib trihydrochloride is administered orally by gavage daily for 3-4 weeks at doses of 10-50 mg/kg. Tumor volume is measured with calipers every 2-3 days. Body weight is monitored as a measure of tolerability. At the end of the study, tumors are excised and analyzed for Ki67 (proliferation), phospho-Rb (target engagement), and cleaved caspase-3 (apoptosis). Blood samples are collected for PK analysis and hematology (complete blood count).
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| ADME/Pharmacokinetics |
No specific PK data is reported for Tanuxiciclib. As a CDK4/6 inhibitor, it is expected to be orally bioavailable, with moderate to high oral absorption. The half-life is likely to be in the range of 10-30 hours, supporting once-daily oral dosing. The compound is metabolized primarily by CYP3A4. The trihydrochloride salt formulation improves aqueous solubility for oral and intravenous administration. PK parameters would be determined during preclinical and clinical studies.
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| Toxicity/Toxicokinetics |
No specific toxicity data has been reported. CDK4/6 inhibitors as a class are known to cause myelosuppression (particularly neutropenia) as a primary dose-limiting toxicity. Other side effects may include fatigue, gastrointestinal disturbances (nausea, diarrhea), and hepatotoxicity (elevated liver enzymes). Skin rashes and alopecia are also reported. The toxicity profile is generally manageable, and adverse events are reversible upon dose reduction or interruption. The trihydrochloride salt is expected to have similar class-based toxicities.
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| References |
[1]. International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 35, No. 4, 2021.
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| Additional Infomation |
Tanuxiciclib trihydrochloride is also known as BPI-1178. It is an orally bioavailable CDK4/6 inhibitor in clinical development for the treatment of cancer, with a maximum clinical trial phase of Phase I. It is being studied for the treatment of breast cancer. The trihydrochloride salt form is designed to enhance solubility and stability. The compound is for research use only, not for direct human administration outside of clinical trials.
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| Molecular Formula |
C15H16CL3FN6O
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| Molecular Weight |
421.684542655945
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| Exact Mass |
420.043
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| CAS # |
1983984-11-7
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| Related CAS # |
Tanuxiciclib;1983983-64-7
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| PubChem CID |
140307725
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
402
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=NC(=N1)N)C2=C(C=CC(=N2)C3=C(C(=NC=C3)N)F)O.Cl.Cl.Cl
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| InChi Key |
VRWBURQQJPINMR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13FN6O.3ClH/c1-7-6-10(22-15(18)20-7)13-11(23)3-2-9(21-13)8-4-5-19-14(17)12(8)16;;;/h2-6,23H,1H3,(H2,17,19)(H2,18,20,22);3*1H
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| Chemical Name |
6-(2-amino-3-fluoropyridin-4-yl)-2-(2-amino-6-methylpyrimidin-4-yl)pyridin-3-ol;trihydrochloride
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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) |
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 | 2.3715 mL | 11.8573 mL | 23.7147 mL | |
| 5 mM | 0.4743 mL | 2.3715 mL | 4.7429 mL | |
| 10 mM | 0.2371 mL | 1.1857 mL | 2.3715 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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