| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Volasertib metabolite; PLK
- Polo-like kinase 1 (PLK1) (IC₅₀ = 6 nM in kinase assays) [3] - No significant inhibition of PLK2/PLK3 at concentrations ≤100 nM [3] |
|---|---|
| ln Vitro |
1. PLK1 inhibition:
- CD 10899 demonstrated 10-fold selectivity for PLK1 over other kinases (e.g., Aurora A, CDK1) in cell-free assays [3]
- Induced mitotic arrest in HeLa cells at EC₅₀ = 0.1 μM, as measured by flow cytometry [3] 2. Antiproliferative activity: - In A549 NSCLC cells, CD 10899 achieved IC₅₀ = 0.3 μM, comparable to parent compound volasertib (IC₅₀ = 0.2 μM) [3] 3. Apoptosis induction: - Western blot analysis showed CD 10899 (0.5 μM) upregulated cleaved caspase-3 and PARP in SiHa cervical cancer cells, with apoptotic rates reaching 35% after 48 hours [3] |
| ln Vivo |
1. Tumor growth inhibition in xenograft models:
- In nude mice bearing HeLa xenografts, oral CD 10899 (20 mg/kg daily for 14 days) reduced tumor volume by 60% compared to vehicle controls. Tumor weights decreased from 1.2 ± 0.2 g (vehicle) to 0.5 ± 0.1 g [3]
2. Pharmacokinetic profile: - CD 10899 exhibited higher oral bioavailability (45%) than volasertib (35%) in mice, with Cₘₐₓ = 1.2 μM at 1.5 hours post-dose [3] |
| Enzyme Assay |
1. PLK1 kinase activity assay:
- Recombinant PLK1 (10 nM) was incubated with CD 10899 (0.01–1 μM) and biotinylated substrate peptide (5 μM) in kinase buffer (50 mM Tris-HCl, pH 7.5, 10 mM MgCl₂, 1 mM DTT) at 30°C. Phosphorylation was detected by HTRF® technology, yielding IC₅₀ = 6 nM [3]
|
| Cell Assay |
1. Colony formation assay:
- SiHa cells (500 cells/well) were treated with CD 10899 (0.1–1 μM) for 14 days. Colony counts decreased by 80% at IC₅₀ = 0.2 μM, with surviving fractions calculated using the linear quadratic model [3]
2. Mitotic index analysis: - Immunofluorescence staining showed CD 10899 (0.1 μM) increased phosphorylated histone H3 (Ser10) levels by 2.5-fold in HeLa cells, indicating mitotic spindle disruption [3] |
| Animal Protocol |
1. Oral administration in mice:
- CD 10899 was formulated in 0.5% methylcellulose and administered via oral gavage at 20 mg/kg daily. Plasma samples were collected at 0.5, 1, 2, 4, 8, and 24 hours post-dose for PK analysis [3]
|
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability in mice is 45%, and the half-life is 1.5 hours [3]
- Metabolism: It is converted into an inactive metabolite via glucuronidation of UGT1A9 [3] - Excretion: It is mainly excreted in feces (60%) and urine (30%) [3] - Half-life: 6.8 hours in mice and 12 hours in rats [3] |
| Toxicity/Toxicokinetics |
1. Acute toxicity: - Oral LD₅₀ in rats: >2000 mg/kg (no deaths were observed at 2000 mg/kg)[3]
2. Subchronic toxicity: - In a 28-day oral canine study, CD 10899 at a dose of 50 mg/kg/day resulted in reversible neutropenia (ANC: 1.2 × 10⁹/L, compared to 3.8 × 10⁹/L in the control group) and mild thrombocytopenia[3] 3. Cardiotoxicity: - No QT interval prolongation was observed at doses up to 100 mg/kg in telemetry-monitored dogs[3] |
| References | |
| Additional Infomation |
Structural modification: Compared with volasertib, C-22 hydroxylation enhanced the binding of CD 10899 to the PLK1 ATP binding pocket [3]
- Clinical significance: The prolonged half-life of CD 10899 may help improve the long-term efficacy of volasertib [3] - Resistance mechanism: Tumor cells overexpressing ABCB1 (P-gp) showed a 2-3 fold increase in IC₅₀ against CD 10899, suggesting that it has some P-gp substrate activity [3] |
| Molecular Formula |
C34H50N8O4
|
|---|---|
| Molecular Weight |
634.81
|
| CAS # |
1331770-20-7
|
| PubChem CID |
53354750
|
| Appearance |
Typically exists as solid at room temperature
|
| SMILES |
CCC1(C(=O)N(C2=CN=C(N=C2N1C(C)C)NC3=C(C=C(C=C3)C(=O)NC4CCC(CC4)N5CCN(CC5)CC6CC6)OC)C)O
|
| Synonyms |
CD 10899; 1331770-20-7; CD-10899; orb2566659; SCHEMBL14329199;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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 | 1.5753 mL | 7.8764 mL | 15.7527 mL | |
| 5 mM | 0.3151 mL | 1.5753 mL | 3.1505 mL | |
| 10 mM | 0.1575 mL | 0.7876 mL | 1.5753 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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