| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
IC50: 0.23 μM (CDK11A in NanoBRET assay), 0.27 μM (CDK11B in NanoBRET assay), 135 nM (CDK4/cyclin D1 in Adapta activity assay), 189 nM (CDK9/cyclin T1 in Adapta activity assay), 217 nM (CDK6/cyclin D1 in Adapta activity assay)[1] Kd: 69 nM (CDK11A in KdELECT assay)[1]
ZNL-05-044 targets cyclin-dependent kinase 11 (CDK11), specifically both the A and B isoforms (CDK11A and CDK11B). In NanoBRET assays, it exhibits IC50 values of 0.23 microM for CDK11A and 0.27 microM for CDK11B. The compound has a Kd of 69 nM for CDK11A in KdELECT assays. It also shows activity against CDK4/cyclin D1 (IC50 = 135 nM), CDK9/cyclin T1 (IC50 = 189 nM), and CDK6/cyclin D1 (IC50 = 217 nM) in Adapta activity assays, indicating some off-target CDK activity. Its primary mechanism is CDK11 inhibition. |
|---|---|
| ln Vitro |
In vitro, ZNL-05-044 inhibits CDK11A and CDK11B with IC50 values of 0.23 microM and 0.27 microM, respectively, as determined by NanoBRET assays. Treatment with ZNL-05-044 leads to G2/M cell cycle arrest and impairs RNA splicing, consistent with known CDK11 functions in spliceosome assembly and cell cycle progression. The compound also inhibits CDK4, CDK9, and CDK6 at higher concentrations, contributing to its anti-proliferative effects. ZNL-05-044 is used to study the role of CDK11 in cancer cell proliferation and survival.
|
| ln Vivo |
In vivo activity data for ZNL-05-044 are not extensively published in the provided sources. As a potent CDK11 inhibitor, it has the potential to suppress tumor growth in animal models of cancer, particularly those driven by CDK11 overexpression or spliceosome dysregulation. Further in vivo studies are required to evaluate its pharmacokinetic properties and anti-tumor efficacy. The compound is expected to cause cell cycle arrest and apoptosis in tumor tissues.
|
| Enzyme Assay |
The in vitro inhibitory activity of ZNL-05-044 against CDK11 is determined using NanoBRET Target Engagement assays. HEK293 cells expressing a NanoLuc-CDK11 fusion protein are seeded in white 96-well plates. The cells are treated with varying concentrations of ZNL-05-044 (0.001-100 microM) for 2 hours at 37degC. A NanoBRET tracer (e.g., a CDK-specific fluorescent tracer) is then added, followed by incubation for an additional 2 hours. After equilibration, NanoBRET Nano-Glo substrate is added, and BRET signals are measured using a plate reader. The BRET ratio is calculated as the emission at 460 nm divided by the emission at 600 nm. The IC50 for target engagement is calculated from the dose-response curve. For biochemical kinase assays, a LanthaScreen Eu kinase binding assay or Adapta kinase assay is used. Recombinant CDK11/cyclin D3 is incubated with varying concentrations of ZNL-05-044 (0.001-100 microM) and a fluorescent tracer. After incubation, terbium-labeled anti-GST antibody is added, and TR-FRET signals are measured. IC50 values are determined using nonlinear regression.
|
| Cell Assay |
For cell-based assays, cancer cell lines (e.g., HeLa, MDA-MB-231, HCT116) are seeded in 96-well plates and treated with ZNL-05-044 at concentrations ranging from 0.01-50 microM for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. Cell cycle distribution is analyzed by flow cytometry after propidium iodide staining. RNA splicing impairment can be assessed by RT-PCR or RNA-seq to detect intron retention or splicing defects. Apoptosis is measured by Annexin V/PI staining.
|
| Animal Protocol |
In vivo protocols for ZNL-05-044 are not well-documented. A typical xenograft efficacy study would involve subcutaneous implantation of cancer cells (e.g., HCT116 or MDA-MB-231) into immunodeficient mice. When tumors reach a volume of 100-200 mm3, mice are randomized and treated with ZNL-05-044 via oral gavage or intraperitoneal injection at doses of 10-100 mg/kg, once daily or on a schedule based on pilot studies. Tumor volume is measured with calipers twice weekly. Body weight is monitored as a general indicator of toxicity. At study termination, tumors are excised for analysis of CDK11 target engagement, cell cycle markers, and apoptosis (e.g., Ki67, phosphohistone H3, cleaved caspase-3).
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for ZNL-05-044 are limited. The compound has a molecular weight of 477.41 and a molecular formula of C21H22Cl2N6OS. It is soluble in DMSO at 100 mg/mL. Solubility in aqueous buffers is likely low due to lipophilic characteristics. For in vivo studies, a formulation such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline is commonly used. Researchers should conduct pilot PK studies to determine half-life, Cmax, oral bioavailability, and tissue distribution in their specific animal model. The compound should be stored at 4degC under nitrogen, and in solvent at -80degC for up to 6 months or -20degC for up to 1 month.
|
| Toxicity/Toxicokinetics |
Toxicological data for ZNL-05-044 are limited to in vitro cell viability assays. In cancer cell lines, the compound reduces viability at concentrations consistent with its CDK11 inhibitory activity (IC50 in the low micromolar range). In non-cancerous cell lines, cytotoxicity may be lower, but no specific data are provided. In animal studies, a dose-finding study would be necessary to determine the maximum tolerated dose (MTD). Standard safety precautions for handling research chemicals should be followed.
|
| References | |
| Additional Infomation |
ZNL-05-044 is a research-grade compound and is not approved for clinical use. It is a selective CDK11 inhibitor developed through structure-guided design from a multi-targeted scaffold. CDK11 is an emerging therapeutic target in oncology due to its essential roles in RNA splicing and cell cycle progression. ZNL-05-044 causes G2/M cell cycle arrest and impairs RNA splicing, making it a valuable tool for probing CDK11 function in cancer biology. Store as a powder at 4degC under nitrogen or in solvent at -80degC.
|
| Molecular Formula |
C21H22CL2N6OS
|
|---|---|
| Molecular Weight |
477.41
|
| Appearance |
White to off-white solid powder
|
| 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) |
DMSO :~100 mg/mL (~209.46 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 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: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0946 mL | 10.4732 mL | 20.9464 mL | |
| 5 mM | 0.4189 mL | 2.0946 mL | 4.1893 mL | |
| 10 mM | 0.2095 mL | 1.0473 mL | 2.0946 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
