| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
WZ811 (WZ-811; WZ 811) is a highly potent, selective, competitive antagonist of CXCR4 chemokine receptor with potential anticancer activity. It has subnanomolar potency (EC50 = 0.3 nM) to inhibit CXCR4 in an affinity binding assay. WZ811 effectively blocks the modulation of cyclic adenosine monophophate (cAMP) levels (EC50 = 1.2 nM) and SDF-1-induced Matrigel invasion (EC50 = 5.2 nM) by CXCR4/stromal cell-derived factor-1 (SDF-1).
| Targets |
CXCR4 ( EC50 = 0.3 nM )
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
Initial Screening of Anti-CXCR4 Small Molecules Based on a Binding Affinity Assay. For compound screening based on a competition binding assay, 2 × 104 MDA-MB-231 cells in 200 μL of medium were seeded in an 8-well slide chamber 2 days before the experiments. Various concentrations of different compounds (1, 10, 100, and 1000 nM) were added to the separate wells and incubated for 10 min at room temperature, and then the cells were fixed in 4% ice-cold paraformaldehyde. The cells were rehydrated in phosphate-buffered saline (PBS) and blocked to eliminate nonspecific binding (avidin and biotin blocking solution). The slides were subsequently incubated for 45 min at room temperature with 0.05 μg/mL biotinylated 3, washed three times with PBS, and incubated in streptavidin-rhodamine (1:150 dilution) for 30 min at room temperature. Finally, the slides were washed with PBS and mounted in an antifade mounting solution, and the samples were analyzed on a Nikon Eclipse E800 microscope[1].
|
|
| Cell Assay |
WZ811 is applied to cells and left for 24 hours at 37°C. Following the process of collection and washing with phosphate-buffered saline (PBS) buffer, the cells are reconstituted at a final density of 1 × 106/mL using staining buffer. Then, 100 μL cell suspensions are mixed with 5 μL annexin V-APC, and the mixture is incubated for 10 minutes at room temperature in the dark. Lastly, FACS Calibur is used to analyze the cell apoptosis profiles.
Tumor Cell Invasion Assay. [1] To model in vitro metastasis, a Matrigel invasion assay was performed within a Matrigel invasion chamber from BD Biocoat Cellware. SDF-1α (200 ng/mL) was added to the bottom chamber to induce the invasion of MDA-MB-231 cells through the Matrigel. The selected compounds were added to the cells before the cells were seeded in the top chamber. The Matrigel invasion chamber was incubated for 22 h in a humidified tissue culture incubator. First, noninvading cells were removed from the top of the Matrigel with a cotton tipped swab. Invading cells at the bottom of the Matrigel were fixed in methanol and stained with hematoxylin and eosin (H&E). The invasion rate was determined by counting the H&E stained cells. cAMP Assay to Measure Gi Function.[1] Perkin-Elmer's LANCE cAMP assay kit based on time-resolved fluorescence resonance energy transfer (TR-FRET) was utilized to determine a compound's ability to block cAMP modulation induced by CXCR4/SDF-1 interaction. Human glioma U87 cells overexpressing CD4 and CXCR4 (U87CD4CXCR4) were seeded at 2500 cells/well in a 384-well plate in 2% FBS 48 h before the test. The experiment was performed according to the manufacturer's instructions using 5 μM Forskolin to induce cAMP production that is reduced by the presence of SDF-1. Results were measured in a Perkin-Elmer Envision 2102 multilabel reader with the following parameters: flash energy area = low, flash energy level = 239, counting cycle = 1 ms, and ex/em = 340 nm/665 nm. |
|
| Animal Protocol |
|
|
| References | ||
| Additional Infomation |
In light of a proposed molecular mechanism for the C-X-C chemokine receptor type 4 (CXCR4) antagonist 1 (AMD3100), a template with the general structure 2 was designed, and 15 was identified as a lead by means of an affinity binding assay against the ligand-mimicking CXCR4 antagonist 3 (TN14003). Following a structure−activity profile around 15, the design and synthesis of a series of novel small molecular CXCR4 antagonists led to the discovery of 32 (WZ811). The compound shows subnanomolar potency (EC50 = 0.3 nM) in an affinity binding assay. In addition, when subjected to in vitro functional evaluation, 32 efficiently inhibits CXCR4/stromal cell-derived factor-1 (SDF-1)-mediated modulation of cyclic adenosine monophophate (cAMP) levels (EC50 = 1.2 nM) and SDF-1 induced Matrigel invasion (EC50 = 5.2 nM). Molecular field topology analysis (MFTA), a 2D quantitative structure−activity relationship (QSAR) approach based on local molecular properties (Van der Waals radii (VdW), atomic charges, and local lipophilicity), applied to the 32 series suggests structural modifications to improve potency.
|
| Molecular Formula |
C18H18N4
|
|
|---|---|---|
| Molecular Weight |
290.3623
|
|
| Exact Mass |
290.15
|
|
| Elemental Analysis |
C, 74.46; H, 6.25; N, 19.30
|
|
| CAS # |
55778-02-4
|
|
| Related CAS # |
|
|
| PubChem CID |
11565518
|
|
| Appearance |
White solid powder
|
|
| Density |
1.2±0.1 g/cm3
|
|
| Boiling Point |
493.2±35.0 °C at 760 mmHg
|
|
| Melting Point |
192-194℃
|
|
| Flash Point |
252.1±25.9 °C
|
|
| Vapour Pressure |
0.0±1.3 mmHg at 25°C
|
|
| Index of Refraction |
1.693
|
|
| LogP |
2.99
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
4
|
|
| Rotatable Bond Count |
6
|
|
| Heavy Atom Count |
22
|
|
| Complexity |
272
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
KBVFRXIGQQRMEF-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C18H18N4/c1-3-11-19-17(5-1)21-13-15-7-9-16(10-8-15)14-22-18-6-2-4-12-20-18/h1-12H,13-14H2,(H,19,21)(H,20,22)
|
|
| Chemical Name |
N-[[4-[(pyridin-2-ylamino)methyl]phenyl]methyl]pyridin-2-amine
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.44 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (3.44 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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 1.5mg/ml (5.17mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4440 mL | 17.2200 mL | 34.4400 mL | |
| 5 mM | 0.6888 mL | 3.4440 mL | 6.8880 mL | |
| 10 mM | 0.3444 mL | 1.7220 mL | 3.4440 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
COA